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Alanineaminotransferase(serum,plasma)

1.1

1.2

1.3

1.4

1.5

2.1

2.2

3.1

Nameanddescriptionofanalyte
Nameofanalyte
Alanineaminotransferase(ALT)
Alternativenames
SystematicnameLalanine:2oxoglutarateaminotransferase(EC2.6.1.2);
alsopyruvateaminotransferase,glutamatepyruvateaminotransferase;
formerlyknownasalaninetransaminase.

NLMCcode
Descriptionofanalyte
ALTisanintracellularcytoplasmicenzyme.Itiswidelydistributed
throughoutthebodystissues,withthegreatestamountsinliverandthe
kidneys.

Functionofanalyte
ALTcatalysesthetransferofaminogroupsfromalanine(forming
pyruvate)to2oxoglutarate(formingglutamate).Itisakeyenzymein
gluconeogenesis.
ALTpresentintheplasmaispresumedtobederivedfromthenormal
turnoveroftissuecells;increasedquantities(theenzymeisusually
assayedbymeasuringitsactivity,see4.1)arefoundintissuedamage
(particularlyhepaticdamage).Itisnotknowntohaveanyfunctionin
plasma.

Samplerequirementsandprecautions
ALTismeasuredinplasmaorserum.
Generalprecautionsonly.
Summaryofclinicalusesandlimitationsofmeasurements
Uses
ALTisusedtoidentifyliverdamagee.g.arisingfromlivercell
inflammationornecrosis.Itsclassificationasaliverfunctiontest(LFT)is
erroneousbuthasbecomeacceptedusageandseemslikelytoprevail.
AlthoughALTiswidelydistributed,significantincreasesinitsplasma
activityarerarelyseenotherthaninliverdisease.Itmaybemeasured
bothinpatientswithclinicalfeaturessuggestiveofliverdiseaseandin
patientsatriskofdevelopingliverdisease.
Thislattercategoryincludesindividualswith:
ahighalcoholintake
ahistoryorknownorpossibleexposuretohepatitisviruses
obesityordiabetes
ahistoryofconsumptionofpotentiallyhepatotoxicdrugs
afamilyhistoryofliverdisease.

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3.2

4.1

Limitations
AnincreaseinALTisanindicatorof(hepatic)tissuedamage;thehighest
valuesareseenintoxicdamagee.ginducedbyacetaminophen
(paracetamol)poisoning,butanincreasedoesnotonitsownprovideany
informationaboutthecauseofthatdamage(thoughsee10.1).
Analyticalconsiderations
Analyticalmethods
Incommonwiththemethodsusedformeasuringmostenzymesfor
clinicalpurposes,ALTisassayedbymeasuringitscatalyticactivity,notits
mass.
TheALTreactioninvolvesanaminoacidandanoxoacidbothas
substratesandproducts.Quantitationmakesuseoftheformationofthe
oxoacid(pyruvate),usinglactatedehydrogenase(lactate:NAD+
oxidoreductase,EC1.1.1.27)toreduceitwithNADHtoformlactate.The
reactionisfollowedbymeasuringthedecreaseinabsorbanceat340nm.

Alanine+2oxoglutarate(ALT)pyruvate+glutamate
Pyruvate+NADH+H+(LD)lactate+NAD+

4.2
4.3

4.4
4.5

Pyridoxine5phosphateisacoenzymefortheALTreaction;itsaddition
tothereactionmixtureensuresthatalltheapoenzymeiscatalytically
activeandmeasured.Preincubationisrequiredtoremoveany
endogenousoxoacidsfromthereactionmixture,thereactionthenbeing
startedbytheadditionof2oxoglutarate.

Referencemethod
Thisisbasedonthemethoddescribedin4.1.

Referencematerials
IRMM(InstituteforReferenceMethodsandMaterials)/IFCC
(InternationalFederationofClinicalChemistry454.

Interferingsubstances
Interferencebyendogenousoxoacidsiseliminatedasdescribedin(4.1).

Sourcesoferror
Aswithallassaysinvolvingmeasurementofenzymeactivity,strict
controlofreactionconditions,especiallytemperature,isessential.

Referenceintervalsandvariance

5.1.1 Referenceinterval:(adultsandchildren)34U/L(female),45U/L(ale)
5.1.2 Referenceintervals(others):valuesaboveapplicabletoallages
5.1.3 Extentofvariation
5.1.3.1 InterindividualCV:24%
5.1.3.2 IntraindividualCV:16%
5.1.3.3 Indexofindividuality:0.66
5.1.3.4 CVofmethod:12.5%
5.1.3.5 Criticaldifference:65%

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5.1.4 Sourcesofvariation:thehighlevelsofintraandinterindividualvariation
reflectthefactthatnormalplasmalevelsaredeterminedbycellturnover
andnotsubjecttoanyformoffeedbackcontrol.

6
Clinicalusesofmeasurementandinterpretationofresults

6.1 Usesandinterpretation

1.See3.1.ALTismeasuredasanindexofliverdamageforwhichitis

more specificthanaspartateaminotransferase(AST).Values>20xthe

upperlimitofnormalmayoccurwithsevereliverdamage.Smaller

increments(usually<5xULN)mayoccurincholestasis,duetosecondary

damagetohepatocytes.

2.Inestablishedliverdisease,afallingALTvalueusuallyreflects

decreasingcelldamage,butmayoccasionallybeaconsequenceofsuch

massivedestructionthat,withclearanceoftheenzyme,evencontinuing

damagedoesnotmaintainhighlevels.
3.Inthecontextofliverdisease,measuringbothALTandASTprovides
littleadditionalinformationoverthatprovidedbymeasuringeitherone.
Therearetwoexceptions:infattyliverdisease,anactivityratioAST/ALT
of>2suggestsalcoholasacause;aratioof1issuggestiveofanon
alcoholiccause.

6.2 Confoundingfactors

None

7 Causesandinvestigationofabnormalresults

7.1 Highvalues
7.1.1 Causes

1.Hepatobiliarydisease
Livercellnecrosis(e.g.inviralhepatitis,toxicliverdamage);values
maybe>20xupperlimitofnormal(ULN).
Cholestaticandotherformsofhepatiobiliarydisease;valuesrarely
exceed5xULNunlessthereisaccompanyinglivercellnecrosis.
2.Extrahepaticdisease
Relativetoplasma,theactivityofALTinvarioustissuesis:liver,
2850x,kidneys,1200x,heart450x,skeletalmuscle300x.Small
increasesinplasmaALTactivitymaythereforeoccurinacutekidney
injury,myocardialinfarctionorskeletalmuscledamage,butthe
increaseinaspartateaminotransferase(AST)activityinthese
conditionsisusuallyhigher.

7.1.2 Investigation

AlthoughALTshouldonlybemeasuredwhenhepatobiliarydiseaseis

suspectedonclinicalgrounds,inpracticeitisfrequentlymeasuredaspart

ofapaneloftestsliverfunctiontests(butsee3.1).However,chronicliver

diseasecanpresentnonspecificallysothatALTmeasurementis

frequentlyrequestedintheabsenceofclassicfeaturesofliverdisease

(e.g.jaundice).Theimportantpracticalquestionmaythenariseastothe

actiontobetakenifanunexpectedlyhighALTvalueisfound.
Foranyvalue,ahighalcoholintake,diabetesorhypertriglyceridaemia
(allofwhichcancausefattyliver)shouldbeexcluded;ifpresent,these
shouldbemanagedappropriatelybeforerepeatingthetest.
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Forincreases2xULN,andotherLFTsnormal,repeatin12months.
Ifrepeatvalue3xULN,furtherinvestigationisrequired.
Values>3xULNfurtherinvestigationisrequiredwithoutrepeat
testingirrespectiveofresultsofotherLFTs.
Firstlinefurtherinvestigationmaycomprise:hepatitisvirusserology,full
bloodcount(foralcoholrelatedmacrocytosisorthrombocytopaenia
secondarytohypersplenismcausedbyportalhypertension),autoimmune
serology(antimitochondrialandantismoothmuscleantibodies),ferritin
(forhaemochromatosis)andhepaticultrasound.Ifthesedonotprovidea
diagnosis,testsforWilsonsdisease,alpha1antityrpsindeficiencyand
coeliacdiseaseshouldbeconsidered.

7.2 Lowvalues

Thelowerreferencelimitiszero:lownormalvaluesareofno

significance.
7.2.1 Investigation

Notrequired.

7.3 Notes

8
Performance

8.1
Sensitivity,specificityetc.forindividualconditions
1.GarciaMonzonC,MartinPerezE,IaconoOLetal.Characterizationof
pathogenicandprognosticfactorsofnonalcoholicsteatohepatitis
associatedwithobesity.JHepatol2000;33:716724.Datasuggestthata
cutoffof40U/Lidentifiesasymptomaticpatientswithhepaticsteatosis
withasensitivityof45%andspecificityof100%;forsteatohepatitis,the
respectivevaluesare45%and64%.
2.SorbiD,BoyntonJ,LindonKD.Theratioofaspartateaminotransferase
toalanineaminotransferase:potentialvalueindifferentiating
nonalcoholicsteatohepatitisfromalcoholicliverdisease.AmJ
Gastroenterol1999;94:10181022.AnALT/ASTratio1.3provided
sensitivityandspecificityof75%forthediagnosisofnonalcoholic
steatohepatitis(NASH)inpatientswitheitherNASHoralcoholicliver
disease;thecorrespondingfiguresforaratioof2.0wereapproximately
100%and50%.
3.GianniniE,RissoD,BottaFetal.Validityandclinicalutilityofthe
aspartateaminotransferasealanineaminotransferaseratioinassessing
diseaseseverityandprognosisinpatientswithhepatitisCvirusrelated
chronicliverdisease.ArchInternMed.2003;163:218224.Oneof
numerousstudiessuggestingthatachangeinthevalueoftheALT/AST
ratiofrom>1(normal)to<1hashighsensitivityfordiagnosingcirrhosisin
patientswithchronichepatitisBorCinfection.

9
Systematicreviewsandguidelines

9.1
Systematicreviews
1.FraserA,HarrisR,SattarNetal.DiabetesCare.2009;32:741750.Epub
2009Jan8.Alanineaminotransferase,gammaglutamyltransferase,and
incidentdiabetes:theBritishWomen'sHeartandHealthStudyandmeta
analysis.Thissystematicreviewemphasisestheimportanceof
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investigationsfordiabetesinindividualsfoundtohaveelevatedserumALT
activities(see7.1).
2.GeboKA,HerlongHF,TorbensonMSetal.Roleofliverbiopsyin
managementofchronichepatitisC:asystematicreview.Hepatology
2002;36(Suppl.1):S161172.DatasuggestthatALTpredictsfibrosisin
chronichepatitisCinfectionwithasensitivityofapproximately65%and
specificityof6694%.

9.2 Guidelines

Noneidentified.

9.3 Recommendations

TherearerecommendationsformeasuringALTinpatientsonvarious

drugs (e.g.statins,glitazones):themanufacturersliteratureshouldbe

consultedforfutherinformation.

10
Links

10.1Relatedanalytes
Aspartateaminotransferase(AST)isalsousedasanindicatoroftissue
damage;itismorewidelydistributedthanALTandthuslessspecificfor
theliver.

10.2 Relatedtests
ALTisusuallymeasuredaspartofapanelofliverfunctiontests(orliver
profile)(butsee3.1)typicallyincludingserumbilirubinandalbumin
concentrationsandalkalinephosphataseactivity.Aspartate
aminotransferase(AST)mayalsobeincluded,butalthoughcomparisonof
ALTandASTactivityinaratio(see8.1)mayprovidehelpfulinformation,
theinclusionofbothenzymesinaroutineliverprofileisofdoubtful
value(asistheroutineinclusionofgammaglutamyltransferase(GGT)in
aliverprofile).

Author:WilliamMarshall

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