8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation

HepatitisATreatment&Management
Author:RichardKGilroy,MBBS,FRACPChiefEditor:BSAnand,MDmore...

Updated:Jan28,2016

ApproachConsiderations
Treatmentgenerallyinvolvessupportivecare,withspecificcomplicationstreatedas
appropriate.Livertransplantation,inselectedcases,isanoptionifthepatienthas
fulminanthepaticfailure(FHF).

PatientsatriskofdevelopingacutehepatitisAvirus(HAV)infectionshouldundergo
immunizationforthevirus.Inaddition,immunizationofthoseatgreaterriskfor
morbidityfromacuteHAVinfectionisimportant.

AGermanstudyofimmunizationratesinpatientswithautoimmuneliverdisease
identifiedthatseroconversionratesinthispopulationwerelowerhowever,more
importantly,thestudyidentifiedthatvaccinationwasnotofferedtoalarge
proportionofthispopulation. [18]Itisnotdifficulttoidentifyalowriskbenefitratioin
patientswithchronicliverdisease,andtheauthorrecommendsvaccinationforHAV
inallwhohavenocontraindication.

Theadventofnewantiviralagents,suchasdirectactingantivirals(DAAs)andhost
targetingagents(HTAs),hasexpandedthepotentialtherapeuticoptionsavailable
againstHAV. [19]Kandaetalnotedthatamantadineandinterferonlambda1(IL29)
inhibitHAVinternalribosomalentrysite(IRES)mediatedtranslationandHAV
replication,whereasJanuskinase(JAK)inhibitorsinhibitLaproteinexpression,
HAVIRESactivity,andHAVreplication. [19]

Seethefollowingformoreinformation:

AlcoholicHepatitis
AutoimmuneHepatitis
CutaneousManifestationsofHepatitisC
HepatitisA
HepatitisB
HepatitisC
HepatitisD
HepatitisE
HepatitisinPregnancy
http://emedicine.medscape.com/article/177484treatment 1/7
8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation

PediatricHepatitisA
PediatricHepatitisB
PediatricHepatitisC
ViralHepatitis

SupportiveCare
ForacutecasesofHAVinfection,therapyisgenerallysupportive,withnospecific
treatmentofacuteuncomplicatedillness.Locatingtheprimarysourceand
preventingfurtheroutbreaksareparamount.Initialtherapyoftenconsistsofbed
rest.Thepatientshouldprobablynotworkduringtheacutephaseoftheillness.

Nauseaandvomitingaretreatedwithantiemetics.Dehydrationmaybemanaged
withhospitaladmissionandintravenous(IV)fluids.Inmostinstances,
hospitalizationisunnecessary.Themajorityofchildrenhaveminimalsymptoms
adultsaremorelikelytorequiremoreintensivecare,includinghospitalization.

About38%ofcasesoffulminanthepaticfailure(FHF)arecausedbyHAV
however,only12%ofHAVinfectionsinadultsleadtoFHF.Referpatientswith
FHFtofacilitieswithexpertiseinlivertransplantation.

Acetaminophenmaybecautiouslyadministeredbutisstrictlylimitedtoamaximum
doseof34g/dayinadults.Othertreatmentsaredirectedbyspecificcomplications.

LiverTransplantation
Patientswithfulminanthepaticfailure(FHF)areconsideredforlivertransplantation.
Recurrentdiseaseafterlivertransplantationhasnotbeenreported.Patient
selectionforlivertransplantationmaybedifficult,inthat60%ofpatientsrecover
fromFHFwithoutneedingthetransplant(muchaswithacetaminophentoxicity),
andpredictingwhoneedsthislifesavingprocedureisdifficult.

Latereferralhasominousimplications,withtheaccompanyingcomorbidities(eg,
renalfailure,coagulopathy,cerebraledema)andwaitingtimescontributingtopoor
outcomes.

LivertransplantationforchronicrelapsingHAVinfectionhasoccurredinthecontext
ofdecompensationwithgoodresultshowever,thereisareportofclinical
recurrenceafterlivertransplantation.

PostexposureProphylaxis
PassiveimmunizationwithGammagardreducesinfectionwhenadministeredwithin
14daysofexposure(ie,postexposureprophylaxis).Recommendationsforproviding
postexposureprophylaxisaredevelopedonthebasisofrisk.

Postexposureprophylaxisisrecommendedfornonimmunizedclosecontactsof
http://emedicine.medscape.com/article/177484treatment 2/7
8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation
thoserecentlydiagnosedwithacuteHAVinfection.Theappropriatepublichealth
authorityshouldbenotifiedafteradiagnosisofHAVinfection,andtheprocessof
contacttracingshouldbeinitiated.IntheUnitedStates,asmanyas10%ofcases
ofacuteHAVinfectionareseenincommercialfoodhandlers.Inanysuspected
foodhandlertransmission,itisimperativethathealthdepartmentofficialsbe
notifiedimmediately.

Inmanyinstances,preexposureprophylaxishasbeensomewhatreplacedby
immunization(seeImmunization).Fortravelers,costbenefitanalysissuggeststhat
vaccinationispreferredovergammaglobulinwhenanextendedstayintheareaof
risk(ie,highendemicity)islongerthan3monthsorwhenrepeattraveltothearea
(ie,>2visitsoutsidea3moperiod)islikely.

Immunization
VaccinationishighlyeffectiveatpreventingHAVdisease.Theefficacyofthe
hepatitisAvaccinerangesfrom80%to100%after12dosescomparedtoplacebo.
Currentdosingrecommendationsareavailable(seeMedication).

Immunizationisindicatedforindividualstravelingtoareasofhighendemicitywho
havelessthan2weeksbeforedeparture.Boththevaccinationandintramuscular
(IM)immunoglobulinshouldbeadministeredtoprovidelongtermimmunity,
particularlyinpersonswhointendtotraveltotheseareasrepeatedly.

PeoplewithchronicliverdiseaseofanycauseshouldconsiderhepatitisA
vaccination.Responseratesinpatientswithadvancedliverdiseaseandinthoseon
immunosuppressivetherapiesarelikelytobelower.Thepotentiallydisastrous
outcomeofacuteHAVinfectioninthisgroupcannotbeoveremphasized.

HepatitisAvaccinationinsomelowriskgroupswhoarepotentialsourcesoflarger
outbreaksofinfection(eg,foodhandlers)hasbeenimplementedbysome
employers,althoughcostbenefitanalysisfortheemployerdoesnotseemto
supportsuchmeasures.

EpidemiologicstudiesofcurrentandhistoricalinformationrelatedtohepatitisA
infectionpatternsandriskfactorsshowstrongassociationsbetweensocioeconomic
improvement,increasedwaterandsanitation,anddecreasingHAVinfectionrates.
[20,21]

AreasinwhichatransitionofepidemichepatitisA(childhoodacquisitionveryhigh)
toendemichepatitisAisoccurringwilllikelyleadtoanincreaseinadultacquired
infectionsandthemorbidityassociatedwiththisintheabsenceofvaccination
programs.

Anexcellentillustrationofwhythisislikelyisthatthemostprevalentriskfactorfor
HAVacquisitionintheUnitedStatesisinternationaltravel. [22]Thisstudyalsolends
furthersupporttotheimportanceofvaccinationforinternationaltravelers.Hepatitis
Aisthemostfrequentvaccinepreventablediseaseintravelers,andithasthe

http://emedicine.medscape.com/article/177484treatment 3/7
8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation

highestmortalityandmorbidityratesforanyvaccinepreventableinfectionin
travelers. [23,24,25]

TheglobalburdenofacutecasesofhepatitisAischangingandcertainlyis
decreasinginWesternsocieties. [20]IntheUnitedStates,vaccinationprograms
targetingchildrenduringurbanoutbreakshavedemonstratedsignificantbenefits. [26,
27]Immunizationprogramsappliedtohighriskgroupsshowmorbidityandcost
benefits.Approximately20%ofindividualswithacuteHAVinfectionmayrequire
hospitalization.

A2012Cochranereviewof9studiesincluding732,380participantsreaffirmedthe
benefitofpreexposurevaccination.Datafromthereviewshowthatboththe
inactivatedandliveattenuatedvaccineswereeffectiveforpreexposureprophylaxis
andthateithervaccineprovidedapproximatelya10foldreductioninacute
infectionswhencomparedtoplacebo.Aninterestingsubgroupanalysisofquality
studiesshowedthatifinfectionsweretooccurtheyoccurredinthefirstyear.In
addition,preexposureprophylaxiswascosteffectiveandsharedcomparableriskof
nonseriouslocalandsystemicadverseeventsinthosereceivingtheinactive
vaccinecomparedtothosereceivingtheplacebo.However,therewereinsufficient
dataonthesafetyoftheliveattenuatedvaccinetorenderconclusionsonsafety
andefficacyovertime. [28]

Globalimmunizationappearstobeprohibitivelyexpensive.ThehepatitisAvaccine
isnotyetlicensedforuseinpersonsyoungerthan2years.

DietandActivity
Encouragepatientstohaveanadequatediet.Patientsshouldavoidalcoholand
medicationsthatmayaccumulateinliverdisease.Otherwise,nospecificdietary
restrictionsarenecessary.

Bedrestduringtheacuteillnessmaybeimportant,althoughdatatosupportthis
practicearelacking.Restrictingtransmissionisimportant,especiallyintheearly
phasesoftheillness.Returningtoworkshouldprobablybedelayedfor10days
aftertheonsetofjaundice.

Prevention
Controlatthesource,withtreatmentofcontactstopreventfurthercasesofdisease
istheprimarygoal.Longtermsecondarygoalsincludeimmunization,which
increasesherdimmunityandreducesthelikelihoodoffurtheroutbreaksinhighrisk
communities.Educationabouttransmissionandpreventionoftransmission(eg,
handwashing,safefoodsources)isalsoimportant.

Medication

ContributorInformationandDisclosures
http://emedicine.medscape.com/article/177484treatment 4/7
8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation

Author
RichardKGilroy,MBBS,FRACPAssociateProfessor,MedicalDirectorofLiverTransplantationand
Hepatology,DepartmentofInternalMedicine,KansasUniversityMedicalCenter

Disclosure:Receivedsalaryfromgilead,NPSpharmaceuticals,salixpharmaceuticals,AbbVieforspeakingand
teaching.

SpecialtyEditorBoard
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference

Disclosure:ReceivedsalaryfromMedscapeforemployment.for:Medscape.

ChiefEditor
BSAnand,MDProfessor,DepartmentofInternalMedicine,DivisionofGastroenterology,BaylorCollegeof
Medicine

BSAnand,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationfortheStudyofLiver
Diseases,AmericanCollegeofGastroenterology,AmericanGastroenterologicalAssociation,AmericanSociety
forGastrointestinalEndoscopy

Disclosure:Nothingtodisclose.

AdditionalContributors
GeorgeYWu,MD,PhDProfessor,DepartmentofMedicine,Director,HepatologySection,HermanLopata
ChairinHepatitisResearch,UniversityofConnecticutSchoolofMedicine

GeorgeYWu,MD,PhDisamemberofthefollowingmedicalsocieties:AmericanAssociationfortheStudyof
LiverDiseases,AmericanGastroenterologicalAssociation,AmericanMedicalAssociation,AmericanSocietyfor
ClinicalInvestigation,AssociationofAmericanPhysicians

Disclosure:ReceivedconsultingfeefromSpringerforconsultingReceivedconsultingfeefromGileadforreview
panelmembershipReceivedhonorariafromVertexforspeakingandteachingReceivedhonorariafromBristol
MyersSquibbforspeakingandteachingReceivedroyaltyfromSpringerforreviewpanelmembershipReceived
honorariafromMerckforspeakingandteaching.

Acknowledgements
SandeepMukherjee,MB,BCh,MPH,FRCPCAssociateProfessor,DepartmentofInternalMedicine,Section
ofGastroenterologyandHepatology,UniversityofNebraskaMedicalCenterConsultingStaff,Sectionof
GastroenterologyandHepatology,VeteranAffairsMedicalCenter

SandeepMukherjee,MB,BCh,MPH,FRCPCisamemberofthefollowingmedicalsocieties:RoyalCollegeof
PhysiciansandSurgeonsofCanada

Disclosure:MerckHonorariaSpeakingandteachingIkariaPharmaceuticalsHonorariaBoardmembership

References
http://emedicine.medscape.com/article/177484treatment 5/7
8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation

1.LongattiA.ThedualroleofexosomesinhepatitisAandCvirustransmissionandviralimmuneactivation.
Viruses.2015Dec17.7(12):670715.[Medline].

2.LiuW,ZhaiJ,LiuJ,XieY.IdentificationofrecombinationbetweensubgenotypesIAandIBofhepatitisA
virus.VirusGenes.2010Apr.40(2):2224.[Medline].

3.KaplanG,TotsukaA,ThompsonP,etal.IdentificationofasurfaceglycoproteinonAfricangreenmonkey
kidneycellsasareceptorforhepatitisAvirus.EMBOJ.1996Aug15.15(16):428296.[Medline].

4.WheelerC,VogtTM,ArmstrongGL,etal.AnoutbreakofhepatitisAassociatedwithgreenonions.N
EnglJMed.2005Sep1.353(9):8907.[Medline].

5.WasleyA,GrytdalS,GallagherK,CentersforDiseaseControlandPrevention(CDC).Surveillancefor
acuteviralhepatitisUnitedStates,2006.MMWRSurveillSumm.2008Mar21.57(2):124.[Medline].

6.AnsaldiF,BruzzoneB,RotaMC,etal.HepatitisAincidenceandhospitalbasedseroprevalenceinItaly:a
nationwidestudy.EurJEpidemiol.2008.23(1):4553.[Medline].

7.DominguezA,BrugueraM,PlansP,etal.DeclininghepatitisAseroprevalenceinadultsinCatalonia
(Spain):apopulationbasedstudy.BMCInfectDis.2007.7:73.[Medline].

8.AggarwalR,GoelA.HepatitisA:epidemiologyinresourcepoorcountries.CurrOpinInfectDis.2015Oct.
28(5):48896.[Medline].

9.KanyendaTJ,AbdullahiLH,HusseyGD,KaginaBM.EpidemiologyofhepatitisAvirusinAfricaamong
personsaged110years:asystematicreviewprotocol.SystRev.2015Sep26.4:129.[Medline].

10.ChobeLP,ArankalleVA.InvestigationofahepatitisAoutbreakfromShimlaHimachalPradesh.IndianJ
MedRes.2009Aug.130(2):17984.[Medline].

11.CaoJ,WangY,SongH,etal.HepatitisAoutbreaksinChinaduring2006:applicationofmolecular
epidemiology.HepatolInt.2009Jun.3(2):35663.[Medline].[FullText].

12.KamathSR,SathiyasekaranM,RajaTE,SudhaL.ProfileofviralhepatitisAinChennai.IndianPediatr.
2009Jul.46(7):6423.[Medline].

13.FischerGE,ThompsonN,ChavesSS,etal.TheepidemiologyofhepatitisAvirusinfectionsinfourPacific
Islandnations,19952008.TransRSocTropMedHyg.2009Sep.103(9):90610.[Medline].

14.AminJ,GilbertGL,EscottRG,etal.HepatitisAepidemiologyinAustralia:nationalseroprevalenceand
notifications.MedJAust.2001Apr2.174(7):33841.[Medline].

15.CooksleyWG.WhatdidwelearnfromtheShanghaihepatitisAepidemic?.JViralHepat.2000May.7
Suppl1:13.[Medline].

16.MofensonLM,BradyMT,DannerSP,etal.Guidelinesforthepreventionandtreatmentofopportunistic
infectionsamongHIVexposedandHIVinfectedchildren:recommendationsfromCDC,theNational
InstitutesofHealth,theHIVMedicineAssociationoftheInfectiousDiseasesSocietyofAmerica,the
PediatricInfectiousDiseasesSociety,andtheAmericanAcademyofPediatrics.MMWRRecommRep.
2009Sep4.58:1166.[Medline].[FullText].

http://emedicine.medscape.com/article/177484treatment 6/7
8/7/2016 HepatitisATreatment&Management:ApproachConsiderations,SupportiveCare,LiverTransplantation

17.KodaniM,MixsonHaydenT,DrobeniucJ,KamiliS.Rapidandsensitiveapproachtosimultaneous
detectionofgenomesofhepatitisA,B,C,DandEviruses.JClinVirol.2014Oct.61(2):2604.[Medline].

18.WornsMA,TeufelA,KanzlerS,etal.IncidenceofHAVandHBVinfectionsandvaccinationratesin
patientswithautoimmuneliverdiseases.AmJGastroenterol.2008Jan.103(1):13846.[Medline].

19.KandaT,NakamotoS,WuS,etal.Directactingantiviralsandhosttargetingagentsagainstthehepatitis
Avirus.JClinTranslHepatol.2015Sep28.3(3):20510.[Medline].

20.JacobsenK,WiermanS.HepatitisAvirusseroprevalencebyageandworldregion.19902005.Vaccine.
2010.28(41):66536657.

21.JacobsenKH,KoopmanJS.DeclininghepatitisAseroprevalence:aglobalreviewandanalysis.Epidemiol
Infect.2004Dec.132(6):100522.[Medline].[FullText].

22.KlevensRM,MillerJT,IqbalK,etal.TheevolvingepidemiologyofhepatitisaintheUnitedStates:
incidenceandmolecularepidemiologyfrompopulationbasedsurveillance,20052007.ArchInternMed.
2010Nov8.170(20):18118.[Medline].

23.CostasL,VilellaA,TrillaA,etal.VaccinationstrategiesagainsthepatitisAintravelersolderthan40
years:aneconomicevaluation.JTravelMed.2009SepOct.16(5):3448.[Medline].

24.MaranoC,FreedmanDO.Globalhealthsurveillanceandtravelers'health.CurrOpinInfectDis.2009Oct.
22(5):4239.[Medline].

25.AsklingHH,RomboL,AnderssonY,MartinS,EkdahlK.HepatitisAriskintravelers.JTravelMed.2009
JulAug.16(4):2338.[Medline].

26.CentersforDiseaseControlandPrevention(CDC).National,state,andlocalareavaccinationcoverage
amongchildrenaged1935monthsUnitedStates,2008.MMWRMorbMortalWklyRep.2009Aug28.
58(33):9216.[Medline].

27.CentersforDiseaseControlandPrevention(CDC).Hepatitisavaccinationcoverageamongchildrenaged
2435monthsUnitedStates,2006and2007.MMWRMorbMortalWklyRep.2009Jul3.58(25):68994.
[Medline].

28.IrvingGJ,HoldenJ,YangR,PopeD.HepatitisAimmunisationinpersonsnotpreviouslyexposedto
hepatitisA.CochraneDatabaseSystRev.2012Jul11.7:CD009051.[Medline].

29.PetrignaniM,VerhoefL,VennemaH,etal.UnderdiagnosisoffoodbornehepatitisA,TheNetherlands,
20082010(1.).EmergInfectDis.2014Apr.20(4):596602.[Medline].

MedscapeReference2011WebMD,LLC

http://emedicine.medscape.com/article/177484treatment 7/7