NoninvasiveDiagnosisandStagingofLiverDisease

NaveenGara,MD

Outline•Briefoverviewoftheanatomyofliver• Liver-relatedlabtests•Chronicliverdiseaseprogression• Estimationofliverfibrosis•Non-invasivemeansofliverfibrosisevaluation• Summary

Liver

MooreKL,Dalley AF.Clinicallyorientedanatomy,4th edition:Philadelphia:LippincottWilliams&Wilkins,1999:268

Liver-relatedLabs

• AspartateAminotransferase(AST)• AlanineAminotransferase(ALT)• AlkalinePhosphatase• GammaGlutamyl Transpeptidase (GGT)• Bilirubin• Albumin• Prothrombintime(PT/INR)• Plateletcount

CausesofChronicLiverDisease

• ChronicViralHepatitis(B,C)• AlcoholicLiverDisease• NonalcoholicFattyLiverDisease• AutoimmuneLiverDiseases(AutoimmuneHepatitis,PrimaryBiliaryCholangitis,PrimarySclerosing Cholangitis)• InheritedMetabolicDefects(Hemochromatosis,WilsonDisease,Alpha-1-antitrypsindeficiency,etc.)• Other

ProgressionofChronicLiverDisease

Pellicoro A,RamachandranPetal;NatureReviewsImmunology14;181-194(2014)

StagingofLiverFibrosis

Faria S,Ganesan K,etal.MRimagingofliverfibrosis:currentstateofart;2009;Oct;29(6);1615-35

LiverBiopsy• Percutaneous• Transjugular• Laparoscopic• EUS-guided

http://www.mayoclinic.org/tests-procedures/liver-biopsy/multimedia/liver-biopsy/img-20007146

LiverBiopsy

Benefits Risks Pitfalls:1. Samplingerror2. Subjectivebias3. Impracticabilityin

obtainingserialbiopsies

NoninvasiveAssessmentofLiverFibrosis

Serologictools:• AST/ALTratio• ASTtoPlateletratioindex(APRI)• FIB-4• Forns index• FibroSure• FibroScore• FibroSpect• FibroMeter• ELFscore

Imagingtools:• Traditionalmodalities

(Ultrasound,CT,MRI)• Newertechniques(Transient

Elastography,AcousticRadiationForceImpulseImaging&MagneticResonanceElastography)

APRI

WaiCT,Greenson JK,etal.AsimplenoninvasiveindexcanpredictbothcirrhosisandadvancedfibrosisinchronichepatitisC;Hepatology;2003;Aug;38(2):518-26

HigherAPRIscorepredictiveofadvancedfibrosisAPRI<1=no/mildfibrosis;APRI>2=cirrhosis

SerologicToolsforFibrosisAssessment

HigherAPRIscorepredictiveofadvancedfibrosisAPRI<1=no/mildfibrosis;APRI>2=cirrhosis

Vallet-Pichard A,etal.FIB-4:aninexpensiveandaccuratemarkeroffibrosis.Hepatology 2007;46;32-6

Koda Metal.Fibroindex,apracticalindexforpredictingsignificantfibrosisinptswithchronichep C.Hepatology;2007;45;297-306

Cross-sectionalImaging

Ultrasound:heterogeneoustexture CT:nodularlivercontourBabu SA,etal.Elastography inchronicliverdisease.Radiographics 2016

Cross-sectionalImaging

CT:Caudatelobehypertrophy MRI:Dilatedportalvein

Babu SA,WellsM,etal.Elastography inchronicliverdisease:Modalities,techniques,limitationsandfuturedirections.Radiographics;2016;36;1987-2006

Cross-sectionalImagingPitfalls:• Lackofobjectivity• Inabilitytodiagnoselesserdegreesoffibrosis• Evencirrhosiscanbemissedwhengrosschangesinliverarenotevidentonimaging• Subtlesignsofcirrhosishavelowinter-readeragreement

TransientElastographyResultsinKPaRange:2.5-75KPa

TapperEB,Afdhal NH.Noninvasiveassessmentofdiseaseprogression.Zakim &Boyer’sTextbookofHepatology;6th edition

TransientElastography

Castera L,Vergniol J,etal.Prospectivecomparisonoftransientelastography,Fibrotest,APRI&liverbiopsyfortheassessmentoffibrosisinchronichepatitisC.Gastro.2005.Feb,128(2):343-50

FS>7.1KPa – advancedfibrosis FS>12.5KPa – cirrhosis

TransientElastography

Pitfalls:• Failuretoobtainavalidresult(obesity,narrowintercostalspaces,etc.)• Canbespuriouslyhighduringahepatitisflare• Onthecontrary,TransientElastography canalsohelpdiagnosecirrhosisinpatientsunder-stagedbybiopsy

GaraN,ZhaoX,etal.Discordanceamongtransientelastography,APRIandhistologicassessmentofliverfibrosisinpatientswithchronichepatitisC;CGH.2013;11(3);303-8.

MagneticResonanceElastography (MRE)

• 3-dimensionalimaging• Potentialtoassessthestiffnessofentireliver• Hightechnicalsuccessinobese&NASHpatientsaswell• Resultsrangefrom0.5to10KPa

• Notavailablewidely• Expensive• Requirestrainedradiologists

MagneticResonanceElastography (MRE)

MRE:focalincreasedstiffness MRIT2W:correspondingconfluentfibrosis

Babu SA,WellsM,etal.Elastography inchronicliverdisease:Modalities,techniques,limitationsandfuturedirections.Radiographics;2016;36;1987-2006

Summary• Chronicliverdiseasefromvariedcausescanleadtoliverfibrosis• Liverbiopsyisconsideredthegoldstandardforfibrosisassessment• Noninvasivetoolshavebeenproventobereliableindifferentiatingbetweenadvancedandnon-advancedfibrosis• APRIisasimpleindexbasedonroutinelabteststhatcanaccuratelydiagnosecirrhosisandadvancedfibrosis• Elastography oftheliverprovidesobjectiveestimatesofliverfibrosisusingeitherultrasoundorMRtechniques