Vous êtes sur la page 1sur 30

OfficialreprintfromUpToDate

www.uptodate.com2017UpToDate

Cirrhosisinadults:Overviewofcomplications,generalmanagement,andprognosis

Authors: EricGoldberg,MD,SanjivChopra,MD,MACP
SectionEditor: BruceARunyon,MD
DeputyEditor: KristenMRobson,MD,MBA,FACG

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2017.|Thistopiclastupdated:Mar07,2017.

INTRODUCTIONCirrhosisrepresentsalatestageofprogressivehepaticfibrosischaracterizedbydistortionofthehepaticarchitecture
andtheformationofregenerativenodules.Itisgenerallyconsideredtobeirreversibleinitsadvancedstages,atwhichpointtheonly
optionmaybelivertransplantation.Inearlierstages,specifictreatmentsaimedattheunderlyingcauseofliverdiseasemayimproveor
evenreversecirrhosis.

Patientswithcirrhosisaresusceptibletoavarietyofcomplications,andtheirlifeexpectancycanbemarkedlyreduced.Cirrhosis
accountedforapproximately49,500deathsandwastheeighthleadingcauseofdeathintheUnitedStatesin2010[1].Inaddition,there
wereanestimated19,500deathsduetolivercancer,whichoftenoccursinthesettingofcirrhosis.Similarly,astudythatuseddatafrom
theNationalDeathIndexfromtheCentersforDiseaseControlandPreventionandtheRochesterEpidemiologyProjectestimatedthat
liverdiseasewasresponsiblefor66,007deathsin2008,ofwhich18,175wereduetohepatobiliarycancer[2].

Thistopicwillreviewthecomplications,generalmanagement,andprognosisofcirrhosis.Anoverviewofthecausesanddiagnosisof
cirrhosisispresentedseparately.(See"Cirrhosisinadults:Etiologies,clinicalmanifestations,anddiagnosis".)

MAJORCOMPLICATIONSMajorcomplicationsofcirrhosisinclude(table1):

Varicealhemorrhage
Ascites
Spontaneousbacterialperitonitis
Hepaticencephalopathy
Hepatocellularcarcinoma
Hepatorenalsyndrome
Hepatopulmonarysyndrome

Oncethesecomplicationsdevelop,patientsareconsideredtohavedecompensatedcirrhosis.Multiplefactorscanpredisposeto
decompensationinapatientwithcirrhosis.Riskfactorsfordecompensationincludebleeding,infection,alcoholintake,medications,
dehydration,andconstipation[35].Inaddition,patientswithobesityareatincreasedriskfordecompensation[6].Oncedecompensation
hasdeveloped,patientsshouldbeconsideredforlivertransplantation.(See"Livertransplantationinadults:Patientselectionand
pretransplantationevaluation"and"Livertransplantationinadults:Patientselectionandpretransplantationevaluation",sectionon
'Cirrhosis'.)

Othermajorcomplicationsofcirrhosisincludeportalveinthrombosisandcardiomyopathy.However,patientswiththesecomplications
alonearenotconsideredtohavedecompensatedcirrhosis.

Thissectionprovidesanoverviewofthecomplicationsofcirrhosis.Theindividualcomplicationsarediscussedindetailintheirrespective
topicreviews.

ComplicationsofportalhypertensionManyofthecomplicationsofcirrhosisaretheresultofportalhypertension(increased
pressurewithintheportalvenoussystem).Thiscanleadtotheformationofvenouscollaterals(varices)aswellascirculatory,vascular,
functional,andbiochemicalabnormalitiesthatcontributetothepathogenesisofascitesandothercomplications.(See"Portalhypertension
inadults"and"Pathogenesisofascitesinpatientswithcirrhosis",sectionon'Portalhypertension'.)

Complicationsofportalhypertensioninclude:

Ascites
Hepaticencephalopathy
Varicealhemorrhage
Spontaneousbacterialperitonitis
Hepatorenalsyndrome
Portalhypertensivegastropathy
Hepatichydrothorax
Hepatopulmonarysyndrome
Portopulmonaryhypertension
Cirrhoticcardiomyopathy
VaricealhemorrhagePatientswithvaricealhemorrhagetypicallypresentwithhematemesisand/ormelena.Itistypicallytreated
withendoscopicvaricealbandligation.Othertreatmentsincludeendoscopicsclerotherapyandplacementofatransjugularintrahepatic
portosystemicshunt(TIPS).(See"Generalprinciplesofthemanagementofvaricealhemorrhage".)

Varicealhemorrhageisassociatedwithhighmortalityrates.Inthepast,themortalityrateofasinglevaricealhemorrhagewas30percent,
andonlyonethirdofpatientssurvivedforoneyear[7,8].Althoughsurvivalhasimprovedwithmoderntechniquesforcontrollingvariceal
hemorrhage,mortalityratesremainhigh(15to20percent30daymortality)[9].

PortalhypertensivegastropathyPortalhypertensivegastropathy(congestivegastropathy),whileextremelycommoninpatients
withportalhypertension,isanuncommoncauseofsignificantbleedinginthesepatients.Whenportalhypertensivegastropathyisthesole
causeofbleeding,thereisdiffusemucosaloozingwithnootherlesions,suchasvarices,toaccountfortheGIbleedingandanemia.The
mucosaisfriable,andbleedingpresumablyoccurswhentheectaticvesselsrupture.Theseverityofgastropathyisrelatedtothelevelof
portalpressure,thelevelofhepaticvascularresistance,andthedegreeofreductioninhepaticbloodflow(See"Portalhypertensive
gastropathy".)

AscitesAscitesistheaccumulationoffluidwithintheperitonealcavity.Itisthemostcommoncomplicationofcirrhosis.Thefirststep
leadingtofluidretentionandultimatelyascitesinpatientswithcirrhosisisthedevelopmentofportalhypertension.Patientswithoutportal
hypertensiondonotdevelopascitesoredema.Thosewithasciteshaveseveralcirculatory,vascular,functional,andbiochemical
abnormalitiesthatcontributetothepathogenesisoffluidretention.(See"Pathogenesisofascitesinpatientswithcirrhosis".)

Ascitesistypicallytreatedwithacombinationofdiureticsandsodiumrestriction,thoughsomepatientsrequirerepeatedtherapeutic
paracentesesorTIPSplacement.Amongpatientswithrefractoryascitesorspontaneousbacterialperitonitis,theuseofnonselectivebeta
blockersmaybeassociatedwithincreasedmortality[10,11].Thismayoccurbecausefailuretomaintainanadequatemeanarterialblood
pressureisstronglycorrelatedwithsurvivalinpatientswithadvancedcirrhosis.(See"Ascitesinadultswithcirrhosis:Initialtherapy"and
"Ascitesinadultswithcirrhosis:Diureticresistantascites",sectionon'Discontinuingbetablockers'and'Decompensatedcirrhosis'below
and"Spontaneousbacterialperitonitisinadults:Treatmentandprophylaxis",sectionon'Discontinuenonselectivebetablockers'.)

SpontaneousbacterialperitonitisSpontaneousbacterialperitonitis(SBP)isaninfectionofpreexistingasciticfluidwithout
evidenceforanintraabdominalsecondarysource,suchasaperforatedviscus.SBPisalmostalwaysseeninthesettingofendstage
liverdisease.ClinicalmanifestationsofSBPincludefever,abdominalpain,abdominaltenderness,andalteredmentalstatus.Some
patientsareasymptomaticandpresentwithonlymildlaboratoryabnormalities.(See"Spontaneousbacterialperitonitisinadults:Clinical
manifestations".)

TheindexofsuspicionforSBPmustbehighwithalowthresholdfordiagnosticparacentesis.Thediagnosisisestablishedbyapositive
asciticfluidbacterialcultureand/oranelevatedasciticfluidabsolutepolymorphonuclearleukocytecount(250cells/mm3).Withoutearly
antibiotictreatment,mortalityishigh.(See"Spontaneousbacterialperitonitisinadults:Diagnosis"and"Spontaneousbacterialperitonitisin
adults:Treatmentandprophylaxis".)

HepatorenalsyndromeHepatorenalsyndromereferstothedevelopmentofrenalfailureinapatientwhohasadvancedliver
diseaseduetocirrhosis,severealcoholichepatitis,acuteliverfailure,orlessoften,ametastatictumor.Ratherthanbeinganewdisease,
hepatorenalsyndromeusuallyrepresentstheendstageofasequenceofreductionsinrenalperfusioninducedbyincreasinglysevere
hepaticinjury.Arterialvasodilatationinthesplanchniccirculation,whichistriggeredbyportalhypertension,appearstoplayacentralrole
inthehemodynamicchangesandthedeclineinrenalfunctioninhepatorenalsyndrome.Theinitialreductionsinglomerularfiltrationrate
areoftenmaskedclinicallysinceassociateddecreasesinmusclemassandhepaticureaproductionminimizeelevationsintheplasma
creatinineconcentrationandbloodureanitrogen.(See"Hepatorenalsyndrome",sectionon'Pathogenesis'.)

Hepatorenalsyndromeischaracterizedbyagenerallybenignurinesediment,averylowrateofsodiumexcretion,andaprogressiverise
intheplasmacreatinineconcentration.Thereissomeconfusionregardingthepresenceorabsenceofoliguria.Thepercentageofpatients
witholiguriadependsuponthecutofffordefiningoliguria.Ifthecutoffis400mL/day,only44percentofpatientsareoliguric.If500
mL/dayisused,approximatelytwothirdsareoliguric.(See"Hepatorenalsyndrome",sectionon'Clinicalpresentation'.)

Thediagnosisisoneofexclusion,beingmadewhenothercausesofrenaldysfunctionhavebeenexcluded.Inparticular,volumedepletion
(aswithoverlyrapiddiuresis)canmimicallofthefindingsofhepatorenalsyndrome.Theprognosisispoorunlesshepaticfunction
improvesoralivertransplantationisperformed.(See"Hepatorenalsyndrome",sectionon'Diagnosis'and"Hepatorenalsyndrome",
sectionon'Treatment'.)

HepatichydrothoraxHepatichydrothoraxisdefinedasthepresenceofapleuraleffusioninapatientwithcirrhosisandno
evidenceofunderlyingcardiopulmonarydisease.Itresultsfromthemovementofasciticfluidintothepleuralspacethroughdefectsinthe
diaphragm,anditisusuallyrightsided.(See"Hepatichydrothorax".)

Thetreatmentforhepatichydrothoraxincludesdiureticsandsodiumrestriction.Patientswhodonotrespondtoconservativetherapymay
requirerepeatedtherapeuticthoracentesesorTIPS.Themostimportantaspectofmanagementisevaluationforlivertransplantation
(algorithm1).Chesttubesshouldnotbeplacedinpatientswithhepatichydrothorax.Placementofchesttubesinthissettingcanresultin
massiveproteinandelectrolytedepletion,infection,renalfailure,andbleeding.

HepatopulmonarysyndromeHepatopulmonarysyndrome(HPS)isdefinedbythefollowingtriad(see"Hepatopulmonary
syndromeinadults:Prevalence,causes,clinicalmanifestations,anddiagnosis"):

Liverdisease
Increasedalveolararterialgradientwhilebreathingroomair
Evidenceforintrapulmonaryvascularabnormalities,referredtoasintrapulmonaryvasculardilatations

EstimatesoftheprevalenceofHPSamongpatientswithchronicliverdiseaserangefrom4to47percent,dependingonthediagnostic
criteriaandmethodsused.EveninthosewithoutHPS,mildhypoxemiaiscommonandispresumablycausedbyascites,withresulting
diaphragmaticelevationandventilation/perfusionmismatch.TherearenoeffectivemedicaltherapiesforHPS.Livertransplantationoffers
themostpromiseforsuccessfultreatment.(See"Hepatopulmonarysyndromeinadults:Naturalhistory,treatment,andoutcomes".)

PortopulmonaryhypertensionPortalhypertensionassociatedpulmonaryhypertension(portopulmonaryhypertension)refersto
thepresenceofpulmonaryhypertensioninpatientswithportalhypertension.Theprevalenceinpatientswithcirrhosisisapproximately2
percent[12].Neithertheprevalencenortheseverityofportopulmonaryhypertensionappearstocorrelatewiththedegreeofportal
hypertension[12].(See"Portopulmonaryhypertension".)

Patientswithportopulmonaryhypertensionmaypresentwithfatigue,dyspnea,peripheraledema,chestpain,andsyncope.Thediagnosis
maybesuggestedbyechocardiographyandconfirmedbyrightheartcatheterization.Patientswithmoderatetosevereportopulmonary
hypertensionaredifficulttotreatwithmedicaltherapy,andtheperioperativemortalitywithlivertransplantationishigh.

CirrhoticcardiomyopathyUpto50percentofpatientswithadvancedcirrhosishavefeaturesofcardiacdysfunction.Theterm
"cirrhoticcardiomyopathy"hasbeenusedtodescribesuchpatients,whoarecharacterizedashavingnormaltoincreasedcardiacoutput
andcontractilityatrest,butabluntedresponsetopharmacologic,physiologic,orpathologicstress[13].Patientsmayalsohave
electrophysiologicabnormalities.Itisthoughttoberelatedtobothportalhypertensionandcirrhosis.Cardiomyopathycanoccurfromany
causeofcirrhosis,althoughpatientswithalcoholismorhemochromatosismayhaveadditionalcontributingcausestocardiacdysfunction.
(See"Highoutputheartfailure",sectionon'Cirrhosis'and"Definitionandclassificationofthecardiomyopathies",sectionon'Cirrhotic
cardiomyopathy'.)

HepaticencephalopathyHepaticencephalopathydescribesthespectrumofpotentiallyreversibleneuropsychiatricabnormalitiesseen
inpatientswithliverdysfunction.Disturbanceinthediurnalsleeppattern(insomniaandhypersomnia)isacommonearlyfeaturethat
typicallyprecedesovertneurologicsigns(figure1andfigure2).Moreadvancedneurologicfeaturesincludethepresenceofasterixis,
hyperactivedeeptendonreflexes,and,lesscommonly,transientdecerebrateposturing.(See"Hepaticencephalopathyinadults:Clinical
manifestationsanddiagnosis".)

Treatmentsforhepaticencephalopathyincludeaddressinganypredisposingconditions(eg,infectionorgastrointestinalbleeding),
syntheticdisaccharides(eg,lactulose),andnonabsorbableantibiotics(eg,rifaximin).(See"Hepaticencephalopathyinadults:Treatment".)

HepatocellularcarcinomaPatientswithcirrhosishaveamarkedlyincreasedriskofdevelopinghepatocellularcarcinoma(HCC).
Patientswithmostformsofchronichepatitisarenotatanincreasedriskuntilcirrhosisdevelops.Exceptionstothisrulearepatientswith
chronichepatitisBvirusinfection,whocandevelopHCCintheabsenceofcirrhosis.(See"Epidemiologyandetiologicassociationsof
hepatocellularcarcinoma"and"Preventionofhepatocellularcarcinomaandrecommendationsforsurveillanceinadultswithchronicliver
disease".)

CertaincausesofcirrhosisappeartohavearelativelyincreasedriskforHCC.PatientswithcirrhosisfromhepatitisB,hepatitisC,
nonalcoholicsteatohepatitis,andhemochromatosisareatthehighestrisk,whilethosewithcirrhosisfromautoimmunehepatitisand
Wilsondiseaseappeartohavealowerrisk.(See"Epidemiologyandetiologicassociationsofhepatocellularcarcinoma",sectionon
'Chronichepatitisandcirrhosis'.)

Becauseofthelargefunctionalreserveoftheliver,patientswithHCCarefrequentlyasymptomaticearlyinitscourse,andthediagnosisis
oftendelayed.DecompensationinapatientwithpreviouslycompensatedcirrhosisshouldraisetheclinicalsuspicionthatHCChas
developed.OthercommonsignsandsymptomsofHCCareusuallyrelatedtomasseffectfromthetumorandincludepain,earlysatiety,
obstructivejaundice,andapalpablemass.HCCscanrupture,causinghemoperitoneum.Paraneoplasticmanifestationsinclude
erythrocytosis,hypercalcemia,hypoglycemia,anddiarrhea.(See"Clinicalfeaturesanddiagnosisofprimaryhepatocellularcarcinoma".)

ThediagnosisofHCCmaybesuggestedbymarkedelevationsofserumalphafetoprotein(AFP)orbycharacteristicradiographic
findings.ElevatedAFPisnotspecificforHCCsinceitcanalsobeseeninpatientswithacuteorchronichepatitis,gonadaltumors,and
pregnancy.However,risingserumAFPlevelsinapatientwithcirrhosisshouldraiseclinicalsuspicionforHCC.However,asignificant
proportionofpatientswithHCChavenormalAFPlevels,especiallywhenthetumorissmall.Asaresult,anormalAFPdoesnotpreclude
adiagnosis.(See"Clinicalfeaturesanddiagnosisofprimaryhepatocellularcarcinoma".)

PortalveinthrombosisPortalveinthrombosiscandevelopinpatientswithcirrhosisandcontributetothedevelopmentofportal
hypertension.Inpatientswithcirrhosis,thepathogenesisislikelyrelatedtounbalancedhemostasisandslowingofportalflow.Treatment
ofteninvolvesanticoagulation,thoughthedecisiontoanticoagulatemusttakeintoaccountthepatient'sriskforbleeding,particularlyif
esophagealvaricesarepresent.(See"Epidemiologyandpathogenesisofportalveinthrombosisinadults",sectionon'Pathogenesis'and
"Acuteportalveinthrombosisinadults:Clinicalmanifestations,diagnosis,andmanagement"and"Chronicportalveinthrombosisinadults:
Clinicalmanifestations,diagnosis,andmanagement".)

GENERALMANAGEMENTThemajorgoalsofmanagingpatientswithcirrhosisinclude:

Slowingorreversingtheprogressionofliverdisease
Preventingsuperimposedinsultstotheliver
Identifyingmedicationsthatrequiredoseadjustmentsorshouldbeavoidedentirely(table2andtable3)
Managingsymptomsandlaboratoryabnormalities
Preventing,identifying,andtreatingthecomplicationsofcirrhosis
Determiningtheappropriatenessandoptimaltimingforlivertransplantation

SlowingorreversingtheprogressionofliverdiseaseAlthoughcirrhosisisgenerallyconsideredtobeirreversibleinitsadvanced
stages,theexactpointatwhichitbecomesirreversibleisunclear[14,15].Somechronicliverdiseasesrespondtotreatmentevenwhen
theliverdiseasehasprogressedtocirrhosis.Thus,specifictherapiesdirectedagainsttheunderlyingcauseofthecirrhosisshouldbe
instituted.

Asexamples:

PatientswithhepatitisCandadvancedfibrosisorcirrhosiswhoachieveasustainedvirologicresponse(SVR)withantiviraltreatment
havealowerriskofliverrelatedmortalitycomparedwithpatientswhodonotachieveanSVR[16].(See"Patientevaluationand
selectionforantiviraltherapyforchronichepatitisCvirusinfection",sectionon'Bridgingfibrosisandcompensatedcirrhosis'.)

Abstinencefromalcoholsubstantiallyimprovessurvivalinalcoholiccirrhosis.(See"Prognosisandmanagementofalcoholicfattyliver
diseaseandalcoholiccirrhosis",sectionon'Abstinence'.)

Successfultreatmentofchronicviralhepatitiscanimprovelongtermoutcomesandmayaffectfibrosis.Inastudyof91patientswith
chronichepatitisCandsignificantfibrosisbasedonliverelastography,patientswhoachievedasustainedvirologicresponsehada
significantdecreaseinliverstiffness(andthuspresumablyfibrosis)24weeksaftertheendoftreatment[17].(See"Noninvasive
assessmentofhepaticfibrosis:Ultrasoundbasedelastography".)

Preventingsuperimposedinsultstotheliver

VaccinationsVaccinationagainsthepatitisAandBforthosewhoarenotalreadyimmunecanhelppreventsuperimposedinsultsto
theliver.Othervaccinations,suchayearlyinfluenzavaccination,arealsorecommended(figure3).(See"Immunizationsforpatientswith
chronicliverdisease".)

AvoidanceofhepatotoxinsPatientswithcirrhosisshouldavoidmedications,supplements,andothersubstancesthatare
commonlyassociatedwithliverinjury.Thisincludesabusedsubstances,suchasalcohol,overthecountermedications(suchas
nonsteroidalantiinflammatorydrugs),prescribeddrugswithhepatotoxicsideeffects,andcertainherbalremedies.(See"Druginduced
liverinjury"and"Hepatotoxicityduetoherbalmedicationsanddietarysupplements".)

MedicationadjustmentsPatientswithcirrhosisareatincreasedriskofadverseeventswithmanymedicationsbecauseofimpaired
hepaticmetabolismorrenalexcretion.Manymedicationsrequiredoseadjustmentsorshouldbeavoidedentirely(table3andtable2)[18].

Issuesrelatedtotheuseofpainmedicationsinpatientswithcirrhosisarediscussedindetailelsewhere.(See"Managementofpainin
patientswithadvancedchronicliverdiseaseorcirrhosis".)

Managementofsymptomsandlaboratoryabnormalities

MusclecrampsPatientswithcirrhosismayexperiencemusclecramps,whichcanbesevere[1922].Thecauseisincompletely
understood,althoughtheymayberelatedtoareductionineffectivecirculatingplasmavolume,nervedysfunction,andalterationsin
energymetabolism[23].Ifotherdisordersareexcluded,treatmentsthatmaybehelpfulincludequininesulfate,branchedchainamino
acids,taurine,zincrepletion(forpatientswithlowlevels),andcorrectionofelectrolytes.Wepreferquininesulfateifpatientsareableto
obtainit(200to300mgatbedtime).(See"Nocturnallegcramps",sectionon'Causesandpathogenesis'.)

Inpatientssuspectedofhavingmusclecrampsrelatedtocirrhosis,othercausesofpainshouldbeexcluded.Musclecrampingrelatedto
cirrhosisisoftenspontaneous,chronic,andnocturnal.Ifthereisnewonsetofpersistentpain,otherdisorderssuchasrhabdomyolysis,
myositis,oracutekidneyinjuryshouldbeconsidered.

Quininesulfatehasbeenfoundtobebeneficialforthetreatmentofmusclecrampsinpatientswithcirrhosis,butitisnolongeravailable
throughpharmaciesfortreatmentofcrampsbecauseofsideeffectsincludingarrhythmiasandthrombocytopenia[24,25].However,itis
availablethroughsomeonlineretailers.Inametaanalysisthatincluded409patientswhocompletedparticipationinrandomizedtrials,
tinnituswastheonlysideeffectthatoccurredmoreoftenwithquininethanwithplacebo.Quininesulfatemayactbyreducingthe
excitabilityofthemotornerve[23].Notethatquininesulfateisnotthesameasquinidinesulfate(thelatterbeinganantiarrhythmicdrug).
(See"Nocturnallegcramps",sectionon'Management'.)

Othertreatmentshaveshownsomebenefitinsmallstudies.Theseincludebranchedchainaminoacids(4ggranulesthreetimesdaily)
[26,27],taurine(3goncedaily)[28,29],andvitaminE(200mgthreetimesdaily)[30].Branchedchainaminoacidsandtaurineare
thoughttoactbycorrectingalterationsinenergymetabolism,andvitaminEisthoughttodecreasecirculatingfreeradicalswithincells.
Correctingelectrolyteabnormalitiesisoftenrecommended,thoughitisnotknownwhetheritimprovessymptoms[23].

Zinchasbeenusedinthepastandmaybebeneficialinpatientswithlowzinclevels,thoughitsroleasatherapeuticagentremains
unclear[23,31].Whenused,ithasbeengivenas220mgtwicedaily.Magnesiumsupplementationhasnotspecificallybeenstudiedin
patientswithliverdisease,butitdoesnotappeartobebeneficialinpatientswithskeletalmusclecrampsingeneral[32].

Onesuggestedapproachtotreatmentis[23]:

Confirmthemusclecrampsarerelatedtocirrhosis
Checkelectrolytelevelsandrepleteiflow
Treatwithbranchedchainaminoacidsifsymptomspersist
Treatwithtaurineifsymptomspersist
TreatwithvitaminEifsymptomspersist

Ourapproachistotreatwithquininesulfateifpatientscanobtainit.Ifnot,webelievetheaboveapproachisareasonablealternative.

UmbilicalherniasUmbilicalherniasposeamanagementdilemmainpatientswithcirrhosis,sincetheyoftendevelopinpatientswith
severeliverdiseaseandasciteswhoareathighriskofcomplicationswithsurgicalrepair[33].Successfulmanagementusingavarietyof
minimallyinvasivesurgicaltechniqueshasbeenreported[3438].However,clinicalexperiencehastemperedourenthusiasmforelective
surgicalrepair.Wehavewitnessedanunacceptablyhighcomplicationandrecurrencerateinourpatientsreferredforelectiverepair[39].
Livertransplantationsurgeonsprefertorepairherniasatthetimeoftransplantationandnotbeforebecausemanyhaveobservedhigh
postoperativemorbidityandmortalitywhenrepairwasperformedbeforethetransplantation.

Wehaveadoptedthefollowingapproachtomanagingumbilicalherniasinpatientswithcirrhosis:

Mostpatientswithrupturedorincarceratedherniasarereferredforimmediaterepair.However,ifincarcerationisdetectedearly,itcan
sometimesbereduced.

Patientswithsymptomaticherniasorthosewithmarkedthinningoftheskinoverlyingtheherniasac(asignofimpendingrupture),
especiallyifthereisweepingoffluidoranescharontheapexofthehernia,arereferredforelectiverepair.

Patientswithasymptomaticherniasaremanagedconservatively,withsurgicalcorrectionoftheherniaperformedatthetimeofliver
transplantation.Thecornerstoneofconservativemanagementinasymptomaticpatientswithumbilicalherniasisaggressive
managementofascites.Elastic/Velcroabdominalbinderscanalsohelpreducepainandminimizefurtherenlargementofthehernia.
(See"Ascitesinadultswithcirrhosis:Initialtherapy"and"Ascitesinadultswithcirrhosis:Diureticresistantascites".)

HyponatremiaHyponatremiaisacommonprobleminpatientswithadvancedcirrhosis.Thepathogenesisofhyponatremiais
directlyrelatedtothehemodynamicchangesandsecondaryneurohumoraladaptationsthatoccurinthesettingofcirrhosis,resultinginan
impairedabilitytoexcreteingestedwater.Theseverityofthehyponatremiaisrelatedtotheseverityofthecirrhosis.Themanagementof
hyponatremiaisdiscussedelsewhere.(See"Hyponatremiainpatientswithcirrhosis",sectionon'Treatment'.)

ThrombocytopeniaorelevatedINRPatientswithcirrhosisfrequentlyhavelowplateletcountsandelevatedinternational
normalizedratios(INRs).Becausethelivermakescoagulationfactorsaswellasanticoagulantproteins,liverdiseasecanleadtoa
hypocoagulablestateorahypercoagulablestate.Therelativebalanceorimbalanceofthesefactorsisnotreflectedinconventionalindices
ofcoagulation,suchastheprothrombintime,activatedpartialthromboplastintime,orINR.(See"Hemostaticabnormalitiesinpatientswith
liverdisease",sectionon'Effectsofhepaticdysfunction'.)

Patientstypicallyonlyneedtreatmentforthrombocytopeniaifaninvasiveprocedurethatisatmoderateorhighriskforbleedingis
planned,orinthesettingofactivebleeding.Itisreasonabletoaimforplateletcountsofatleast50,000/microLduringmoderaterisk
procedures[40]orinterventionsandplateletcountscloserto100,000/microLinhighrisksituationsorinthepresenceofactivebleeding
[41].(See"Hemostaticabnormalitiesinpatientswithliverdisease",sectionon'Invasiveprocedure'.)

Becauseconventionalindicesofcoagulationarenothelpfulindeterminingapatient'sbleedingrisk,patientswhorequireaninvasive
procedurethatisatmoderateorhighriskforbleedingorwhohaveactivebleedingmayneedadditionaltesting,suchasadeterminationof
fibrinogenlevels,thromboelastography,orthromboelastometrytoguidemanagement.Whileplasmaiscommonlygiventopatientswith
chronicliverdiseaseandanelevatedINR,plasmainfusionmayhaveadverseeffectsonportalveinpressuresandcollateralvesselflow.In
addition,thetraditionaldoseoftwounitsofplasmaisunlikelytosignificantlyaltercoagulationfactorlevels.(See"Clinicaluseofplasma
components",sectionon'Plasmaproducts'and"Hemostaticabnormalitiesinpatientswithliverdisease",sectionon'Commonclinical
problems'.)

Themanagementofpatientswithchronicliverdiseasewhorequireaninvasiveprocedurethatisatmoderateorhighriskforbleeding,or
whohaveactivebleeding,isdiscussedindetailelsewhere.(See"Hemostaticabnormalitiesinpatientswithliverdisease",sectionon
'Bleeding'and"Hemostaticabnormalitiesinpatientswithliverdisease",sectionon'Invasiveprocedure'.)

PreventingandidentifyingcomplicationsPatientsshouldbemonitoredforthedevelopmentofcomplications,andwhenpossible,
stepsshouldbetakentopreventtheirdevelopment.Inparticular,patientsshouldbescreenedforesophagealvaricesandhepatocellular
carcinoma.Ifvaricesarepresent,prophylactictreatmentwithbetablockersoresophagealvaricealligationisindicated.

Othermeasurestodecreasetheriskofcomplicationsincludejudiciousdiuresisandavoidingprotonpumpinhibitorsinpatientswithout
clearindicationsfortheiruse(spontaneousbacterialperitonitis)treatinginfections(spontaneousbacterialperitonitis,hepatic
encephalopathy)avoidingsedativesandtreatinghypokalemiaandhyponatremia(hepaticencephalopathy)avoidingnephrotoxicagents
andaggressivediuresis(hepatorenalsyndrome)andonlyusingurinarycatheters,mechanicalventilation,andcentrallineswhenclearly
indicated(secondaryinfections).(See'Majorcomplications'above.)

Varicealbleeding:Allpatientswithcirrhosisshouldundergoscreeningforesophagealvariceswithupperendoscopysothat
prophylactictherapycanbegiventothosewithvaricesthatareatincreasedriskforbleedingandtodeterminetheriskofvariceal
hemorrhage.Prophylactictherapymostcommonlyinvolvestreatmentwithanonselectivebetablockerorendoscopicvaricealligation,
whichreducestheriskofvaricealbleeding.(See"Primaryandpreprimaryprophylaxisagainstvaricealhemorrhageinpatientswith
cirrhosis".)

Hepatocellularcarcinoma:Patientswithcirrhosisshouldundergosurveillancewithultrasonographyeverysixmonths.(See
"Preventionofhepatocellularcarcinomaandrecommendationsforsurveillanceinadultswithchronicliverdisease",sectionon
'Surveillancemethods'.)

Spontaneousbacterialperitonitis:Theriskofspontaneousbacterialperitonitis(SBP)canbereducedbyeffortstodiuresepatients
sincediuresisconcentratesasciticfluid,therebyraisingasciticfluidopsonicactivity.Earlyrecognitionandaggressivetreatmentof
localizedinfections(eg,cystitis,cellulitis)canalsohelptopreventbacteremiaandSBP.Protonpumpinhibitorusehasbeen
associatedwithanincreasedriskofSBP,soprotonpumpinhibitorsshouldonlybegiventopatientswhohaveclearindicationsfor
theiruse.Finally,prophylacticantibioticsaimedatdecontaminatingtheguthavearoleinspecificclinicalsettings.(See"Spontaneous
bacterialperitonitisinadults:Treatmentandprophylaxis".)

Hepaticencephalopathy:Patientswithcirrhosisshouldbeevaluatedregularlyforhepaticencephalopathy,theearliestfeaturesof
whichcanbesubtle.Eventsthatcanprecipitatehepaticencephalopathyincludethedevelopmentofvaricealbleeding,infection(such
asSBP),theadministrationofsedatives,hypokalemia,andhyponatremia,allofwhichshouldbecorrected/avoidedwhenever
possible(table4).(See"Hepaticencephalopathyinadults:Clinicalmanifestationsanddiagnosis"and"Hepaticencephalopathyin
adults:Treatment".)

Portalveinthrombosis:Enoxaparinmaybeeffectiveforpreventingportalveinthrombosis(PVT)inpatientswithcirrhosis,thoughit
isnotusedroutinely.Ifitistobeused,wesuggesteradicationofvarices(ifpresent)priortoinitiationofanticoagulationwhen
possible.(See"Chronicportalveinthrombosisinadults:Clinicalmanifestations,diagnosis,andmanagement",sectionon'Prevention
inpatientswithcirrhosis'and"Primaryandpreprimaryprophylaxisagainstvaricealhemorrhageinpatientswithcirrhosis",sectionon
'Endoscopicvaricealligation'.)

Hepatorenalsyndrome:Nephrotoxicagents(suchasaminoglycosides)andvigorousdiuresisshouldbeavoidedinpatientswith
cirrhosissincetheycanprecipitaterenalfailure.(See"Hepatorenalsyndrome".)

Secondaryinfections:Patientswithcirrhosiswhoarehospitalizedoftenacquireinfectionswhileinthehospital.Factorsthathave
beenassociatedwithhospitalacquiredsecondaryinfectionsinpatientswithcirrhosisincludetheuseofurinarycatheters,mechanical
ventilation,andtheplacementofcentrallines[42].Manyoftheseinterventionsareperformedroutinely(suchasplacementofurinary
catheterstomeasureurineoutput).However,avoidingtheseinterventionsunlesstheyareabsolutelynecessarymaydecreasethe
riskofacquiringaninfectionwhileinthehospital,anditisourpracticetoonlyusetheseinterventionswhenclearlyindicated.

Inastudyof207patientswithcirrhosiswhowereadmittedwithordevelopedaninfectionduringhospitalization,50(24percent)
developedasecondinfectionduringhospitalization[42].Respiratoryinfectionswerethemostcommon(14patients),followedby
urinarytractinfections(13patients),andClostridiumdifficile.Oftheurinarytractinfections,6(46percent)wererelatedtotheuseof
bladdercatheters.Otherfactorsassociatedwithsecondinfectionsincludedintensivecareunitadmission,theuseofcentrallines,
mechanicalventilation,shock,renalreplacementtherapy,andhepaticencephalopathy.Overallmortalitywas39percent,butitwas48
percentforthosewhodevelopedasecondinfectionduringadmission.

TreatmentofcomplicationsThetreatmentofthecomplicationsofcirrhosisisdiscussedintherespectivetopicreviews.(See'Major
complications'above.)

LivertransplantationLivertransplantationisthedefinitivetreatmentforpatientswithdecompensatedcirrhosis.Itisimportantto
determinewhetherpatientsmaybeeligiblefortransplantationandtoreferthemtoatransplantcenterforevaluation.Severalguidelines
areavailablewhichhelpdeterminewhenreferralforlivertransplantationmaybebeneficial.Thedecisiontoproceedtolivertransplantation
(eithercadavericorlivedonor)dependsupontheseverityofdisease,qualityoflife,andtheabsenceofcontraindications.(See"Liver
transplantationinadults:Patientselectionandpretransplantationevaluation".)

PROGNOSISTheprognosisofcirrhosisishighlyvariablesinceitisinfluencedbyanumberoffactors,includingetiology,severity,
presenceofcomplications,andcomorbiddiseases.Oncedecompensationoccurs(eg,thepatientdevelopsvaricealbleeding,hepatic
encephalopathy,orspontaneousbacterialperitonitis),mortalityratesarehigh.(See'Decompensatedcirrhosis'below.)

CompensatedcirrhosisPatientswithcirrhosiswhohavenotdevelopedmajorcomplicationsareclassifiedashavingcompensated
cirrhosis.Themediansurvivalofpatientswithcompensatedcirrhosisis>12years[43].Patientswithvaricesbutwhohavenotdeveloped
varicealbleedingareconsideredtohavecompensatedcirrhosis,thoughtheirprognosisisworsethanthatofpatientswhohave
compensatedcirrhosiswithoutvarices(3.4versus1.0percentoneyearmortalityrates)[43].

DecompensatedcirrhosisPatientswhohavedevelopedcomplicationsofcirrhosis,suchasvaricealhemorrhage,ascites,
spontaneousbacterialperitonitis,hepatocellularcarcinoma,hepatorenalsyndrome,orhepatopulmonarysyndrome,areconsideredto
havedecompensatedcirrhosisandhaveaworseprognosisthanthosewithcompensatedcirrhosis.(See'Majorcomplications'above.)

Asystematicreviewfoundthatthemediansurvivalwas6monthsinpatientswithdecompensatedcirrhosisandaChildPughscore12
oraModelforEndstageLiverDisease(MELD)score21[44].Inaddition,patientswithdecompensatedcirrhosiswhohadbeen
hospitalizedwithanacuteliverrelatedillness(eg,varicealhemorrhageorspontaneousbacterialperitonitis)hadamediansurvivalof6
monthsiftheChildPughscorewas12ortheMELDscorewas18.
Animportantfactorrelatedtosurvivalismeanarterialpressure.Inaseriesof139patientswithcirrhosisandascites,ameanarterial
pressureof82mmHgwasanimportantpredictorofsurvival[45].Amongpatientswithameanarterialpressure82mmHg,survivalwas
20percentat24monthsand0percentat48months(comparedwith70and50percent,respectively,forpatientswithameanarterial
pressure>82mmHg).

Anotherfactorthatmaybeassociatedwithsurvivalisthepresenceofrelativeadrenalinsufficiency[46,47].Inastudyof143patientswho
wereadmittedtothehospitalwithdecompensatedcirrhosis,relativeadrenalinsufficiencywasdetectedin37patients(26percent)[46].At
thetimeofpresentation,comparedwithpatientswhodidnothaverelativeadrenalinsufficiency,patientswithrelativeadrenalinsufficiency
hadlowermeanarterialpressures(76versus83mmHg)andserumsodiumlevels(131versus135mEq/L)andhadhigherbloodurea
nitrogenlevels(32versus24mg/dL).Duringthreemonthsoffollowup,patientswithrelativeadrenalinsufficiencyweremorelikelyto
developinfection(41versus21percent),severesepsis(27versus9percent),type1hepatorenalsyndrome(16versus3percent),and
death(22versus7percent).(See"Diagnosisofadrenalinsufficiencyinadults".)

Amongpatientswithcirrhosisandseveresepticshock,administrationofhydrocortisonemayimproveoutcomes[48].(See"Treatmentof
adrenalinsufficiencyinadults",sectionon'Glucocorticoidregimens'.)

Otherfactorsassociatedwithpoorsurvivalinpatientswithdecompensatedcirrhosisincludedhepatopulmonarysyndrome,rapidly
progressivehepatorenalsyndrome,andintensivecareunitadmissionforcomplicationsofliverdiseasealongwithhypotensionrequiring
pressorsupport,serumcreatinine>1.5mg/dL,orjaundice.

Patientswithdecompensatedcirrhosisoftenrequirelivertransplantation.Forthosewhoarenotcandidates,hospicecarecanbe
consideredforpatientswithpredictedsurvivalof6months.(See"Livertransplantationinadults:Patientselectionandpretransplantation
evaluation"and"Benefits,services,andmodelsofsubspecialtypalliativecare".)

PredictivemodelsMultiplestudieshaveattemptedtopredicttheprognosisofpatientswithcirrhosisbasedonclinicalandlaboratory
information.TwocommonlyusedmodelsaretheChildPughclassificationandMELD.

ChildPughclassificationTheChildPughclassification(table5)hasbeenusedtoassesstheriskofnonshuntoperationsin
patientswithcirrhosis(calculator1andcalculator2)[49].ItisamodificationoftheChildTurcotteclassification,whichincorporatedfive
variablesthatweredesignedtostratifytheriskofportacavalshuntsurgeryinpatientswithcirrhosis.Thevariablesincludedtheserum
albuminandbilirubin,ascites,encephalopathy,andnutritionalstatus(table6)[50].TheChildPughclassificationreplacesnutritionalstatus
withprothrombintime.Thescorerangesfrom5to15.Patientswithascoreof5or6haveChildPughclassAcirrhosis(wellcompensated
cirrhosis),thosewithascoreof7to9haveChildPughclassBcirrhosis(significantfunctionalcompromise),andthosewithascoreof10
to15haveChildPughclassCcirrhosis(decompensatedcirrhosis).

Inareviewof92patientswithcirrhosiswhounderwentabdominalsurgery,themortalityratewas10percentforpatientswithChildPugh
classAcirrhosis,30percentforpatientswithChildPughclassBcirrhosis,and82percentforpatientswithChildPughclassCcirrhosis
[51].OtherstudieshavevalidatedtheutilityoftheChildPughclassificationfortheassessmentofsurgicalrisk[52].(See"Assessing
surgicalriskinpatientswithliverdisease".)

TheChildPughclassificationsystemalsocorrelateswithsurvivalinpatientsnotundergoingsurgeryoneyearsurvivalratesforpatients
withChildPughclassA,B,andCcirrhosisareapproximately100,80,and45percent,respectively[53,54].ChildPughclassisalso
associatedwiththelikelihoodofdevelopingofcomplicationsofcirrhosis.Asanexample,patientswithChildPughclassCcirrhosisare
muchmorelikelytodevelopvaricealhemorrhagethanthosewithChildPughclassAcirrhosis[55].

MELDscoreAnothermodeltopredictprognosisinpatientswithcirrhosisistheMELDscore.Itisbaseduponbilirubinlevels,
creatinine,INR,andtheetiologyofcirrhosis(calculator3andcalculator4).TheMELDscorehasbeenadoptedforuseinprioritizing
patientsawaitinglivertransplantationandhasanexpandingroleinpredictingoutcomesinpatientswithliverdiseaseinthenon
transplantationsetting.InJanuary2016,OrganProcurementandTransplantationNetworkPolicy9.1(MELDScore)wasupdatedto
includeserumsodiumasafactorinthecalculationoftheMELDscore[56].TheMELDNascorecanbecalculatedonline.(See"Modelfor
EndstageLiverDisease(MELD)".)

WHENTOREFERTOASPECIALISTReferraltoahepatologistisrecommendedifthepatientdevelopsdecompensatedcirrhosisor
majorcomplicationsofcirrhosis.PatientswithaMELDscore10shouldbereferredtoalivertransplantationcenterforevaluation.In
addition,referraltoahepatologistshouldbeconsideredifthepatientrequirestreatmentfortheunderlyingcauseofthecirrhosis(eg,
hepatitisC,autoimmunehepatitis)oriftheclinicianmanagingthepatientwouldliketheassistanceofahepatologistinthepatient's
generalmanagement.(See"Livertransplantationinadults:Patientselectionandpretransplantationevaluation",sectionon'Cirrhosis'.)

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and"BeyondtheBasics."The
Basicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,andtheyanswerthefourorfivekey
questionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefer
short,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.These
articlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewith
somemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.
(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon"patientinfo"andthekeyword(s)ofinterest.)

Basicstopics(see"Patienteducation:Cirrhosis(TheBasics)"and"Patienteducation:Livercancer(TheBasics)")
BeyondtheBasicstopics(see"Patienteducation:Cirrhosis(BeyondtheBasics)")

SUMMARYANDRECOMMENDATIONS

Cirrhosisrepresentsalatestageofprogressivehepaticfibrosischaracterizedbydistortionofthehepaticarchitectureandthe
formationofregenerativenodules.Itisgenerallyconsideredtobeirreversibleinitsadvancedstages.Inearlierstages,specific
treatmentsaimedattheunderlyingcauseofliverdiseasemayimproveorevenreversecirrhosis.(See'Introduction'above.)

Patientswithcirrhosisaresusceptibletoavarietyofcomplications,andtheirlifeexpectancycanbemarkedlyreduced.Major
complicationsofcirrhosisinclude(see'Majorcomplications'above):

Varicealhemorrhage
Ascites
Spontaneousbacterialperitonitis
Hepaticencephalopathy
Hepatocellularcarcinoma
Hepatorenalsyndrome
Hepatopulmonarysyndrome
Portalveinthrombosis
Cardiomyopathy

Themajorgoalsofmanagingpatientswithcirrhosisinclude(see'Generalmanagement'above):

Slowingorreversingtheprogressionofliverdisease(see'Slowingorreversingtheprogressionofliverdisease'above).
Preventingsuperimposedinsultstotheliver(see'Preventingsuperimposedinsultstotheliver'above).
Identifyingmedicationsthatrequiredoseadjustmentsorshouldbeavoidedentirely(table2andtable3)(see'Medication
adjustments'above).
Managingsymptomsandlaboratoryabnormalities(see'Managementofsymptomsandlaboratoryabnormalities'above).
Preventingandtreatingthecomplicationsofcirrhosis(see'Preventingandidentifyingcomplications'above).
Determiningtheappropriatenessandoptimaltimingforlivertransplantation(see'Livertransplantation'above).

Theprognosisofcirrhosisishighlyvariablesinceitisinfluencedbyanumberoffactors,includingetiology,severity,presenceof
complications,andcomorbiddiseases.Oncedecompensationoccurs(eg,thepatientdevelopsvaricealbleeding,hepatic
encephalopathy,orspontaneousbacterialperitonitis),mortalityratesarehigh.(See'Decompensatedcirrhosis'above.)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

REFERENCES

1.MurrayCJ,AtkinsonC,BhallaK,etal.ThestateofUShealth,19902010:burdenofdiseases,injuries,andriskfactors.JAMA2013
310:591.
2.AsraniSK,LarsonJJ,YawnB,etal.UnderestimationofliverrelatedmortalityintheUnitedStates.Gastroenterology2013145:375.
3.LiaoWC,HouMC,ChangCJ,etal.Potentialprecipitatingfactorsofesophagealvaricealbleeding:acasecontrolstudy.AmJ
Gastroenterol2011106:96.
4.MumtazK,AhmedUS,AbidS,etal.Precipitatingfactorsandtheoutcomeofhepaticencephalopathyinlivercirrhosis.JColl
PhysiciansSurgPak201020:514.
5.SundaramV,ShaikhOS.Hepaticencephalopathy:pathophysiologyandemergingtherapies.MedClinNorthAm200993:819.
6.BerzigottiA,GarciaTsaoG,BoschJ,etal.Obesityisanindependentriskfactorforclinicaldecompensationinpatientswith
cirrhosis.Hepatology201154:555.
7.SmithJL,GrahamDY.Varicealhemorrhage:acriticalevaluationofsurvivalanalysis.Gastroenterology198282:968.
8.GrahamDY,SmithJL.Thecourseofpatientsaftervaricealhemorrhage.Gastroenterology198180:800.
9.D'AmicoG,DeFranchisR,CooperativeStudyGroup.Upperdigestivebleedingincirrhosis.Posttherapeuticoutcomeand
prognosticindicators.Hepatology200338:599.
10.GePS,RunyonBA.Thechangingroleofbetablockertherapyinpatientswithcirrhosis.JHepatol201460:643.
11.MandorferM,BotaS,SchwablP,etal.Nonselectiveblockersincreaseriskforhepatorenalsyndromeanddeathinpatientswith
cirrhosisandspontaneousbacterialperitonitis.Gastroenterology2014146:1680.
12.HadengueA,BenhayounMK,LebrecD,BenhamouJP.Pulmonaryhypertensioncomplicatingportalhypertension:prevalenceand
relationtosplanchnichemodynamics.Gastroenterology1991100:520.
13.ZardiEM,AbbateA,ZardiDM,etal.Cirrhoticcardiomyopathy.JAmCollCardiol201056:539.
14.BonisPA,FriedmanSL,KaplanMM.Isliverfibrosisreversible?NEnglJMed2001344:452.
15.IwaisakoK,BrennerDA,KisselevaT.What'snewinliverfibrosis?Theoriginofmyofibroblastsinliverfibrosis.JGastroenterol
Hepatol201227Suppl2:65.
16.SingalAG,VolkML,JensenD,etal.Asustainedviralresponseisassociatedwithreducedliverrelatedmorbidityandmortalityin
patientswithhepatitisCvirus.ClinGastroenterolHepatol20108:280.
17.HzodeC,CastraL,RoudotThoravalF,etal.LiverstiffnessdiminisheswithantiviralresponseinchronichepatitisC.Aliment
PharmacolTher201134:656.
18.LewisJH,StineJG.Reviewarticle:prescribingmedicationsinpatientswithcirrhosisapracticalguide.AlimentPharmacolTher
201337:1132.
19.AbramsGA,ConcatoJ,FallonMB.Musclecrampsinpatientswithcirrhosis.AmJGastroenterol199691:1363.
20.BaskolM,OzbakirO,CokunR,etal.Theroleofserumzincandotherfactorsontheprevalenceofmusclecrampsinnonalcoholic
cirrhoticpatients.JClinGastroenterol200438:524.
21.AngeliP,AlbinoG,CarraroP,etal.Cirrhosisandmusclecramps:evidenceofacausalrelationship.Hepatology199623:264.
22.KonikoffF,TheodorE.Painfulmusclecramps.Asymptomoflivercirrhosis?JClinGastroenterol19868:669.
23.MehtaSS,FallonMB.Musclecrampsinliverdisease.ClinGastroenterolHepatol201311:1385.
24.CorbaniA,ManousouP,CalvarusoV,etal.Musclecrampsincirrhosis:thetherapeuticvalueofquinine.Isitunderused?DigLiver
Dis200840:794.
25.ManSonHingM,WellsG,LauA.Quininefornocturnallegcramps:ametaanalysisincludingunpublisheddata.JGenInternMed
199813:600.
26.SakoK,ImamuraY,NishimataH,etal.Branchedchainaminoacidssupplementsinthelateeveningdecreasethefrequencyof
musclecrampswithadvancedhepaticcirrhosis.HepatolRes200326:327.
27.HidakaH,NakazawaT,KutsukakeS,etal.Theefficacyofnocturnaladministrationofbranchedchainaminoacidgranulesto
improvequalityoflifeinpatientswithcirrhosis.JGastroenterol201348:269.
28.MatsuzakiY,TanakaN,OsugaT.Istaurineeffectivefortreatmentofpainfulmusclecrampsinlivercirrhosis?AmJGastroenterol
199388:1466.
29.YamamotoS,OhmotoK,IdeguchiS,etal.[Painfulmusclecrampsinlivercirrhosisandeffectsoforaltaurineadministration].Nihon
ShokakibyoGakkaiZasshi199491:1205.
30.KonikoffF,BenAmitayG,HalpernZ,etal.VitaminEandcirrhoticmusclecramps.IsrJMedSci199127:221.
31.KugelmasM.Preliminaryobservation:oralzincsulfatereplacementiseffectiveintreatingmusclecrampsincirrhoticpatients.JAm
CollNutr200019:13.
32.GarrisonSR,AllanGM,SekhonRK,etal.Magnesiumforskeletalmusclecramps.CochraneDatabaseSystRev2012:CD009402.
33.CarbonellAM,WolfeLG,DeMariaEJ.Pooroutcomesincirrhosisassociatedherniarepair:anationwidecohortstudyof32,033
patients.Hernia20059:353.
34.MarsmanHA,HeisterkampJ,HalmJA,etal.Managementinpatientswithlivercirrhosisandanumbilicalhernia.Surgery2007
142:372.
35.OzdenI,EmreA,BilgeO,etal.Electiverepairofabdominalwallherniasindecompensatedcirrhosis.Hepatogastroenterology1998
45:1516.
36.SaritC,EliezerA,MizrahiS.Minimallyinvasiverepairofrecurrentstrangulatedumbilicalherniaincirrhoticpatientwithrefractory
ascites.LiverTranspl20039:621.
37.MelcherML,LobatoRL,WrenSM.Anoveltechniquetotreatrupturedumbilicalherniasinpatientswithlivercirrhosisandsevere
ascites.JLaparoendoscAdvSurgTechA200313:331.
38.BelliG,D'AgostinoA,FantiniC,etal.Laparoscopicincisionalandumbilicalherniarepairincirrhoticpatients.SurgLaparoscEndosc
PercutanTech200616:330.
39.RunyonBA,JulerGL.Naturalhistoryofrepairedumbilicalherniasinpatientswithandwithoutascites.AmJGastroenterol1985
80:38.
40.SeeffLB,EversonGT,MorganTR,etal.Complicationrateofpercutaneousliverbiopsiesamongpersonswithadvancedchronic
liverdiseaseintheHALTCtrial.ClinGastroenterolHepatol20108:877.
41.ArgoCK,BalogunRA.Bloodproducts,volumecontrol,andrenalsupportinthecoagulopathyofliverdisease.ClinLiverDis2009
13:73.
42.BajajJS,O'LearyJG,ReddyKR,etal.Secondinfectionsindependentlyincreasemortalityinhospitalizedpatientswithcirrhosis:the
NorthAmericanconsortiumforthestudyofendstageliverdisease(NACSELD)experience.Hepatology201256:2328.
43.D'AmicoG,GarciaTsaoG,PagliaroL.Naturalhistoryandprognosticindicatorsofsurvivalincirrhosis:asystematicreviewof118
studies.JHepatol200644:217.
44.SalpeterSR,LuoEJ,MalterDS,StuartB.Systematicreviewofnoncancerpresentationswithamediansurvivalof6monthsorless.
AmJMed2012125:512.e1.
45.LlachJ,GinsP,ArroyoV,etal.Prognosticvalueofarterialpressure,endogenousvasoactivesystems,andrenalfunctionin
cirrhoticpatientsadmittedtothehospitalforthetreatmentofascites.Gastroenterology198894:482.
46.AcevedoJ,FernndezJ,PradoV,etal.Relativeadrenalinsufficiencyindecompensatedcirrhosis:Relationshiptoshorttermriskof
severesepsis,hepatorenalsyndrome,anddeath.Hepatology201358:1757.
47.TsaiMH,PengYS,ChenYC,etal.Adrenalinsufficiencyinpatientswithcirrhosis,severesepsisandsepticshock.Hepatology2006
43:673.
48.FernndezJ,EscorsellA,ZabalzaM,etal.Adrenalinsufficiencyinpatientswithcirrhosisandsepticshock:Effectoftreatmentwith
hydrocortisoneonsurvival.Hepatology200644:1288.
49.PughRN,MurrayLyonIM,DawsonJL,etal.Transectionoftheoesophagusforbleedingoesophagealvarices.BrJSurg1973
60:646.
50.Child,CG,III,Turcotte,JG.SurgeryandPortalHypertension.In:TheLiverandportalhypertension,Child,CGIII(Eds),WB
Saunders,Philadelphia1964.p.50.
51.MansourA,WatsonW,ShayaniV,PicklemanJ.Abdominaloperationsinpatientswithcirrhosis:stillamajorsurgicalchallenge.
Surgery1997122:730.
52.GarrisonRN,CryerHM,HowardDA,PolkHCJr.Clarificationofriskfactorsforabdominaloperationsinpatientswithhepatic
cirrhosis.AnnSurg1984199:648.
53.InfanteRivardC,EsnaolaS,VilleneuveJP.Clinicalandstatisticalvalidityofconventionalprognosticfactorsinpredictingshortterm
survivalamongcirrhotics.Hepatology19877:660.
54.AlbersI,HartmannH,BircherJ,CreutzfeldtW.SuperiorityoftheChildPughclassificationtoquantitativeliverfunctiontestsfor
assessingprognosisoflivercirrhosis.ScandJGastroenterol198924:269.
55.deFranchisR,PrimignaniM.Whydovaricesbleed?GastroenterolClinNorthAm199221:85.
56.https://optn.transplant.hrsa.gov/news/meldserumsodiumpolicychanges/.

Topic1263Version32.0
GRAPHICS

Commoncomplicationsofcirrhosis

Varicealhemorrhage

Ascites

Spontaneousbacterialperitonitis

Hepaticencephalopathy

Hepatocellularcarcinoma

Hepatorenalsyndrome

Hepatopulmonarysyndrome

Hepatichydrothorax

Portopulmonaryhypertension

Cirrhoticcardiomyopathy

Portalveinthrombosis

Graphic65667Version3.0
Treatmentsforhepatichydrothorax

Allpatientswithconfirmedhepatichydrothoraxshouldbereferredforevaluation
forlivertransplantation.Thefirststepinmanagementistherapywithlow
sodiumdiet(88mEq[2000mg]perday)anddiuretics(seetopicreviewon
diuretictherapyforascites).Ifthereisnoresponsetodiuretics,therapeutic
thoracentesisofapproximately2literscanbeattemptedfollowedbydiuretics.If
patientsdonotrespondtodiureticsordevelopcomplications,theycanbe
consideredtohaverefractoryhepatichydrothoraxandshouldbeconsideredfor
transjugularintrahepaticportosystemicshunt(TIPS)placement.Thismeasure
mayhelpasabridgetolivertransplantation.However,patientsshouldbe
carefullyselected.TIPSisbestconsideredinpatientsyoungerthan70yearsof
age,withouthepaticencephalopathy,and/orthosewithChildA/Bcirrhosis.For
patientsthatcannotundergoTIPSplacement,considerationforpleurodesisor
diaphragmaticrepairbythoracoscopyshouldbeconsidered.Chesttube
placementshouldbeavoidedasitisassociatedwithseverecomplications.

*Furosemide40mg/dayandspironolactone100mg/day,andifthereisno
response,diureticsmaybeincreasedinastepwisefashioneverythreetofivedays
bydoublingdoses(ratioof40mg:100mg),furosemideupto160mg/dayand
spironolactoneupto400mg/day.

Graphic80148Version4.0
Evolutionofhepaticencephalopathy

Graphic58163Version1.0
Clinicalfeaturesofhepaticencephalopathy

Diagramdepictingthegradeofhepaticencephalopathyandtheclinicalfeaturesassociatedwith
advancingstages.

Datafrom:ConnHO,LieberthalMM.Thehepaticcomasyndromesandlactulose.LippincottWilliams&
Wilkins,Baltimore1979.

Graphic70740Version5.0
Medications(otherthananalgesics*)usedinadultpatientswithadvancedchronicliverdiseaseor
cirrhosis

Alteredresponseandpharmacokinetics Managementsuggestions

Alcoholabstinence

Baclofen Limitedhepaticmetabolism. Totaldailydosetitratedto30to60mg,givenin


Preliminarysafetydataincirrhosisarepromising divideddoses,hasbeentoleratedbypatientswith
however,efficacyisnotwellestablished. cirrhosis.
RefertoUpToDatetopicreviewofascitesinadults
withcirrhosisinitialtherapy,sectiononalcohol
abstinence.

Disulfiram Hepaticallymetabolizedandsubjecttonumerousdrug Avoidorusewithextremecautionincirrhosis.


interactions.
Reportsoffulminanthepatotoxicity.

Anticonvulsants

Carbamazepine Carbamazepineisapotentinducerofhepaticenzymes Ingeneral,carbamazepineshouldbeavoidedasthere


andhasbeenassociatedwithhepatotoxicityand aresaferoptionsformanagementofseizuresin
seriousallergicreactionsingeneticallypredisposed patientswithadvancedCLDorcirrhosis.
individuals.
Mayprecipitatedecompensationinpatentswith
cirrhosis.

Lamotrigine Halflifeisincreaseduptothreefoldinmoderateto Noadjustmentrequiredformildimpairment.


severehepaticimpairment. Reducedoseby25%formoderatetoseverehepatic
impairmentwithoutascites.
Reducedoseby50%formoderatetosevere
impairmentwithascites.

Levetiracetam PKunalteredinliverdiseaseinpatientswithadequate Noadjustmentrequiredforcompensatedcirrhosis.


renalfunction(Crcl60mL/minute). Reducedosebyapproximately50%inpatientswith
Drugaccumulationmayoccurinpatientswithrenal advancedCLDandrenalinsufficiency(Crcl<60
insufficiencyandadvancedcirrhosis. mL/minute).

Oxcarbazepine PKseemstobeunalteredinmildtomoderatehepatic Nospecificadjustmentrecommendedfor


impairmentwithadequaterenalfunction(Crcl30 compensatedcirrhosiswithmildtomoderatehepatic
mL/minute). impairment.
Useinseverehepaticimpairmentordecompensated
diseaseisnotrecommendedasdataarelacking.

Phenytoin Extensivelymetabolizedinliverandapotentinducer Ingeneral,phenytoinshouldbeavoidedinpatients


ofhepaticCYPenzymes. withcirrhosis.
Highlyboundtoserumalbuminhypoalbuminemic Intheabsenceofothereffectiveoptionsforcontrolof
patientswithadvancedCLDorcirrhosisgenerally seizures,usecautiouslyincompensatedcirrhosis.
requirelowertotalplasmaconcentrationsforseizure Avoidinpatientswhoareactivelyusingalcohol.
controlrelativetohealthyindividuals. Freephenytoinlevelsmaybeusefulformonitoring
serumconcentrations.
RefertoUpToDatetopicreviewonpharmacologyof
antiepilepticdrugs.

Topiramate Topiramateclearancecanbereducedinpatientswith Topiramatedoseadjustmentmaybeneededin


advancedCLDorcirrhosiswhoarealsoreceiving patientswithadvancedCLDorcirrhosisreceiving
enzymeinducingantiepilepticdrugsand/orwithrenal enzymeinducingantiepilepticdrugsand/orrenal
insufficiency(Crcl<70mL/minute). impairment.
Metabolicacidosisisafrequentadverseeffectof Druginteractionsbetweentopiramateandenzyme
topiramatetreatment.RefertoUpToDatetopicreview inducingantiepilepticdrugsmaybeintensifiedin
onpharmacologyofantiepilepticdrugs. hepaticimpairment.
Serumconcentrationmonitoringmaybeuseful.

Valproate(valproicacid) Extensivelymetabolizedinliverandhighlyboundto Valproateshouldgenerallybeavoidedinadvanced


serumalbumin. CLDorcirrhosis.
Drugaccumulationandtoxicityhasbeenobservedin Useiscontraindicatedinseverehepaticimpairment.
valproatetreatedpatientswithadvancedCLDor
cirrhosis.
Valproateassociatedhyperammonemiamaycomplicate
managementofHE.

Antidepressants

Bupropion Reducedclearanceandprolongedhalflifein Donotexceed75mgperday(immediaterelease),


alcoholicsandinpatientswithseverehepatic 100mgperday(sustainedrelease),or150mgevery
impairment. otherday(extendedrelease)inpatientswithearlyor
moderatecompensatedcirrhosis.
Avoidinsevereordecompensatedcirrhosisandin
patientsatriskforseizures.

Citalopram ExtensivelymetabolizedinliverbyCYPs2C19and Donotexceed20mgdaily.


3A4.
Exposure(plasmaconcentrationversustimecurve)
increasedtwofoldinsettingofcirrhosis.
Patientswithcirrhosis,particularlyifthereisaTIPS
orsurgicalshuntpresent,maybeatelevatedriskof
developingpotentiallyfatalventriculararrhythmiasdue
toQTprolongation.

Desvenlafaxine MetabolizedinliverprimarilybyUGTglucuronidation. Initiateat50mgdaily.Donotexceed100mgdaily.


PKunalteredinmildhepaticimpairment. Avoidindecompensatedcirrhosis,cirrhosiswithrenal
failure,andinpatientsatriskforseizures.

Duloxetine 85%reductioninclearanceandthreetofivefold AlcoholabuseorCLDmayberiskfactorsinduloxetine


increaseinhalflifeandexposure(plasma associatedhepatotoxicity.
concentrationversustimecurve)inmoderate Useshouldbeavoidedinhepaticimpairment.
cirrhosis.

Escitalopram ExtensivelymetabolizedinliverbyCYPs2C19and Initiateatalowdose(5mgdaily)forfirsttwoweeks


3A4. ormore.
Clearancereducedby37%,halflifeincreased Donotexceed10mgdaily.
approximatelytwofoldinsettingofcirrhosis.

Fluoxetine Reducedclearance. Reducedoseorfrequencyincirrhosisby50%.


Halflifeofactivemetabolitemayexceed12daysin Initiateatalowdose(eg,5or10mgdaily)andtitrate
cirrhosis. graduallytopreventaccumulation.
Newsteadystateconcentrationsmaynotbereached Donotexceed20to40mgdailyinmildhepatic
untiltwoormoremonthsfollowingadose impairment.
adjustment.

Fluvoxamine ExtensivelymetabolizedinliverbyCYP2D6and Reducedoseby50%.


undergoesfirstpassextraction. Initiateatalowdose(eg,25mgdaily)andtitrate
Oralbioavailabilityisincreasedandhalflifeprolonged graduallytopreventaccumulation.
to22to26hoursinsettingofcirrhosis. Donotexceed100mgdaily.

Mirtazapine Halflifeincreasedby40%andexposure(plasma Donotexceed30mgperday.


concentrationversustimecurve)increased
approximately55%inmildtomoderatehepatic
impairment.

Paroxetine ExtensivelymetabolizedinliverbyCYP2D6and Initiateat10mgdailyandtitrategradually.


undergoesfirstpassextraction. Donotexceed40mgdaily.
Halflifeprolongedandexposure(plasma
concentrationversustimecurve)increased
approximatelytwofoldinadvancedCLDorcirrhosis.

Sertraline ExtensivelymetabolizedinliverbyCYP2D6and Initiateat25mgdailyandtitrategraduallytoprevent


undergoesfirstpassextraction. accumulation.
Halflifeprolongedby2.5foldandexposure(plasma Donotexceed100mgdaily.
concentrationversustimecurve)increasedbyupto
fourfoldinadvancedCLDorcirrhosis.

Venlafaxine ExtensivelymetabolizedinliverbyCYP2D6and Initiateatalowdose(eg,37.5to75mgdaily)and


undergoesfirstpasshepaticextraction. titrategraduallytopreventaccumulation.Donot
WideinterindividualPKvariabilityseeninpatients exceed150mgdaily.
withcirrhosis. Avoidindecompensatedcirrhosis,cirrhosiswithrenal
Oralbioavailabilityisincreasedbytwotothreefoldin failure,andinpatientsatriskforseizures.
patientswithmildtomoderatehepaticimpairment.
Halflifeofvenlafaxineanditsactivemetabolitesis
prolongedbyupto1.4foldinmildtomoderate
hepaticimpairment.

Antipsychotics

Haloperidol ComplexhepaticmetabolismincludesCYP3A4and2D6 Nospecificdoseadjustment.


transformationsandactivemetabolites. Avoidwithactivealcoholconsumption.
ConsistentalterationofPKinhepaticimpairmenthas Avoidorusecautionwithalcoholwithdrawal
notbeenidentified. syndromeduetoriskofseizures.
Patientswithcirrhosis,particularlyifthereisaTIPS PreferabletobenzodiazepinesinpatientswithHE.
orsurgicalshuntpresent,maybeatelevatedriskof
developingpotentiallyfatalventriculararrhythmiasdue
toQTprolongation.

Olanzapine UndergoesextensivemetabolisminliverbyCYPs1A2 Inadvancedhepaticimpairmentinitiateorallyat5mg


and2D6. dailyandescalatedose,ifneeded,moregradually.
Halflifeisexpectedtobeincreasedinadvanced
hepaticimpairment.

Quetiapine UndergoesextensivemetabolisminliverbyCYP3A4. Initiateorallyat25mgdaily(immediaterelease)and


Halflifeisexpectedtobeincreasedinadvanced titrateinlowincrements(eg,25to50mgdaily)
hepaticimpairment. accordingtoresponse.

Antiinfectives

Antifungals

Azoles
Azoleantifungalsarevariablymetabolizedinliver,and UseazoleswithcautioninadvancedCLDorcirrhosis.
allhavebeenassociatedwithhepaticfunction Maintenancedosereductionandserumlevel
abnormalities. monitoringarerecommendedforvoriconazole.
Ketoconazole,itraconazole,voriconazole,and Doseoffluconazoleshouldbeadjustedinadvanced
posaconazolehavepotentinhibitoryeffectsonhepatic CLDorcirrhosiswithrenalinsufficiency.
CYPmetabolism. AvoidketoconazoleinpatientswithCLD.
RefertoUpToDatetopicreviewofpharmacologyof
azoleantifungals.

Echinocandins Caspofunginandmicafunginundergohepatic Caspofunginrequiresdoseadjustmentinmoderate


metabolism. CLD.
Anidulafunginisnothepaticallymetabolizedalteration Aspecificdoseadjustmentrecommendationfor
ofPKduetoCLDorrenalinsufficiencyisnot caspofunginisnotavailableforadvancedCLDor
expected. cirrhosis.
Modestasymptomaticincreasesinhepatic Regularmonitoringofhepatictransaminasesis
transaminasesoccurinapproximately10%of suggestedduringechinocandintreatment.
echinocandintreatedpatientswithoutCLD. RefertoUpToDatetopiconpharmacologyof
echinocandins.

Antimicrobials Hydrophilicantimicrobials(ie,aminoglycosides,betalactams,daptomycin,vancomycin)tendtoexhibitincreased
VdinpatientswithadvancedCLDorcirrhosiswithascitesorhypoalbuminemia.Loadingdose(s)andmonitoring
ofbloodconcentrationswhereavailableshouldbeconsideredfortreatingseriouslyillpatients.

Betalactams, Betalactamassociatedleukopeniamaycomplicate Monitorforbetalactamassociatedleukopenia.


carbapenems impairedreticularendothelialcellfunctioninadvanced
CLDorcirrhosis.

Fluoroquinolones Norfloxacin,ciprofloxacin,andlevofloxacinare Norfloxacin,levofloxacin,andciprofloxacindose


eliminatedrenallyanddonotundergoextensive shouldbeadjustedforadvancedCLDorcirrhosiswith
hepaticmetabolism.Levofloxacindistributesinascitic renalimpairment.RefertoLexicompmonographs.
fluid,butlessextensivelythancefotaxime. UsecautioninpatientswithprolongedQTintervals.
Patientswithcirrhosis,particularlyifthereisaTIPS
orsurgicalshuntpresent,maybeatelevatedriskof
developingpotentiallyfatalventriculararrhythmiasdue
toQTprolongation.

Macrolides Extensivelymetabolizedinliver. UseclarithromycinwithcautioninadvancedCLDor


Erythromycinestolate(notavailableinUnitedStates) cirrhosis.
maycausecholestasisinCLD. Avoiderythromycinestolate.
CertainmacrolidescanincreaseQTcinterval.

Metronidazole Metabolizedinliver,reducedclearanceandprolonged Increaseintervaltoevery12hoursinpatientswith


halflife(18to21hours)inadvancedCLDor advancedCLDorcirrhosis.
cirrhosis.

Tetracyclines Tetracyclinesaremetabolizedinliverandhalflifemay Reduceddoseshouldbeconsideredincompensated


beprolongedinadvancedCLDandcirrhosis. disease.
UsecautioninadvancedCLDorcirrhosis.
Ingeneral,avoidtetracyclinesindecompensated
cirrhosis.

Tigecycline Tigecyclineiseliminatedlargelybybiliaryexcretion Doseoftigecyclineshouldbeadjustedinsevere


anddoesnotundergoextensivemetabolisminthe hepaticimpairment.RefertoLexicompmonograph.
liver.

Trimethoprim Renallyexcreted. NodoseadjustmentrecommendedforCLDor


sulfamethoxazole PKappearsunalteredinmildtomoderatehepatic cirrhosiswithmildtomoderatehepaticimpairment.
(cotrimoxazole) impairment. Reducedoseinrenalinsufficiency.
Useshouldbeavoidedinseverehepaticimpairment
anddecompensateddiseaseaccordingtothelicensed
productinformation.

Antituberculosisdrugs IsoniazidmayaccumulateinadvancedCLDand Closelymonitorandconsiderdosereduction.


(isoniazid,pyrazinamide, cirrhosis. RefertoUpToDatetopicontreatmentofpulmonary
rifampin) Rifampiniseliminatedinbileandcanpotentially tuberculosisinHIVnegativepatients.
worsenjaundiceinpatientswithcirrhosisdueto
competitiveexcretoryinhibition.
IncreasedriskofDILI.

HepatitisBantivirals Minorornohepaticmetabolism. NodoseadjustmentnecessaryinCLDorcirrhosis.


(adefovir,entecavir, PKunalteredinCLD. Dosereductionsneededforrenalimpairment.
lamivudine,tenofovir) Safelyusedindecompensatedcirrhosiswhen
treatmentindicated.

HIVantiretrovirals ManagementofHIVantiretroviraltherapyinpatientswithhepaticimpairmentisreviewedseparately.Referto
UpToDatetopicondosemodificationofantiretroviralagentsinadultswithrenalorhepaticdysfunctionand
separatetableinUpToDateonantiretroviraldosingrecommendationsinpatientswithrenalorhepatic
insufficiency.

Antidiabetic

Insulins Insulinsarefrequentlyusedfortreatmentofdiabetes Insulinsaredosedbaseduponeffectwithcloseblood


withCLD. glucosemonitoring.
Metformin UsedsafelyinadvancedCLDandcompensated Ingeneral,agoodchoiceformostdiabeticpatients
cirrhosis. withmildtomoderateCLDandcompensated
Beneficialintreatmentofdiabeteswithvariousforms cirrhosis.
ofCLDincludingNAFLD. Dosemetforminbasedonresponse.
Metforminshouldbeavoidedinpatientswhoconsume
excessivealcoholorwithrenalinsufficiencyor
advancedCLDorcirrhosisduetoriskoflactic
acidosis,ararebutpotentiallyfatalcomplicationof
metformintreatment.

Sulfonylureasand Sulfonylureas(eg,glipizide)arefrequentlyprescribed Sulfonylureasandmeglitinidesaregenerallysafein


meglitinides topatientswithdiabetesandCLD. mildtomoderateCLDandcompensatedcirrhosis
Sulfonylureasandmeglitinides(eg,repaglinide, usinglowestinitialdose,gradualtitrationbasedon
nateglinide)arehepaticallymetabolized,andincreased closemonitoring,andareducedmaintenancedose.
concentrationsincirrhosisareexpected,butspecific Lowdosegliclazide(notavailableinUnitedStates),
dataarelacking. repaglinide,andnateglinidemaybereasonable
choicesduetoshorterdurationofactionandlessrisk
ofhypoglycemiaobservedingeneraldiabetic
population.
Sulfonylureasshouldbeavoidedorusedcautiouslyin
olderadultswithcirrhosisandinpatientswithrenal
insufficiencyandadvancedcirrhosis.

Cardiovascular

Antiarrhythmics Hepaticimpairmentdecreasestheeliminationofmany Dosereductionsareusuallyrequired.


antiarrhythmics. RefertoLexicompindividualdrugmonographs.

Amiodarone Amiodaroneishighlytissueandproteinbound, Dosereductionisexpectedtobenecessaryinhepatic


undergoesextensivehepaticmetabolismbyvarious impairmentandcirrhosis.
CYPsincluding3A4and2C8,andisexcretedfecally Nospecificrecommendationisavailable.
viabile.
Itsextremelylonghalflifeof25to100daysis
expectedtobefurtherprolongedinhepatic
impairment.

Antihypertensives

ACEinhibitors ACEinhibitorsaregenerallywelltolerated. NodoseadjustmentofACEinhibitorsrequiredin


MinorPKdifferencesincirrhosisincludeincreased advancedCLDorcompensatedcirrhosis.
drugbioavailability(ie,lisinopril)orslowed Nonprodrugs(eg,lisinopril)preferredtoprodrugs
conversiontoactivedrugform(ie,enalapril),butdo (eg,quinapril,enalapril).
nottranslatetoamarkedlyalteredresponse. Ifcombinedwithdiuretic,usecautiouslyandin
ACEinhibitorsdonotadequatelydecreaseportal reduceddoses.
venouspressuretoprotectagainstvaricealbleeding. ConsiderdiscontinuingACEinhibitorsinpatientswho
developdiureticresistantascites.RefertoUpToDate
topicreviewsofmanagingascites.

Betablockers PKcharacteristicsandmetabolismofindividualbeta Startatlowdoseandtitratebaseduponclinical


blockersvary. response.
Propranololandmetoprololhaveincreasedoral Carvediloldoseshouldbereducedbyupto80%.
bioavailabilityinadvancedCLDandcirrhosisdueto Nadololandsotalolarenothepaticallymetabolized.
highfirstpassextractionandproteinbinding. Doseadjustmentneededforrenalimpairment.
CarvedilolisextensivelymetabolizedbyCYP,whereas Nadololandpropranololcanbeusedfortreatmentof
nadololandsotalolarenot. portalhypertensionandthepreventionofvariceal
Decreasedtherapeuticeffectofbetaadrenergic hemorrhage.RefertoUpToDatetopicreviewsof
blockadetherapymaybeobservedinsettingof prophylaxisagainstvaricealhemorrhage.
advancedCLDanddecompensatedcirrhosis. Discontinuationofbetablockersmaybenecessaryin
Labetalolusehasbeenassociatedwithhepatoxicity. patientswhodevelopdiureticresistantascites.Refer
toUpToDatetopicreviewsofmanagingascites.
Labetalolisgenerallyavoidedintreatmentofpatients
withcirrhosis.

Calciumchannel Diltiazemoralbioavailabilityisincreased,andhalflife Startoraldiltiazematlowdoseandtitrategradually


blockers oforalandIVareprolongedbyupto50%. basedonresponse.
Oralbioavailabilityofverapamilisdoubled,andhalf Reduceverapamildosebyapproximately50%.
lifeoforalandIVareprolongedbyfourfold. Initiateamlodipineatlowestdose(eg,2.5to5mg)
Amlodipineishighlyproteinboundandundergoes andtitrateatintervalsofnolessthan10to14days
extensivehepaticmetabolismviaCYP3A4.Halflifeis baseduponresponse.
expectedtobeprolonged(56hours)inhepatic
impairment.

Diuretics

Furosemide, Reducednatriureticpotencydependingondisease Furosemideisusuallygivenorallyandgradually


torsemide, severity. titratedtoeffect.
bumetanide Increasedsensitivitytohypokalemiaandvolume Combinationoffurosemidewithspironolactonecan
depletion. mitigateloopdiureticassociatedhypokalemiaand
improvediuresisintreatmentofascites.
RefertoUpToDatetopiconinitialtherapyofascitesin
adultswithcirrhosis.

Spironolactone
Extensivelymetabolizedinliver. Spironolactone100mgperdayincombinationwith
Severalactivemetaboliteswithprolongedhalflifein oralfurosemide40mgperdayissuggestedforinitial
cirrhosispermitoncedailydosingand,insome treatmentofascites.
patients,alternatedaydosing. Spironolactoneandfurosemidearetitratedgradually
Incombinationwithfurosemide,counteracts baseduponresponseusingaratioof100mg
hypokalemiaandimprovesdiuresisintreatmentof spironolactoneto40mgfurosemide.
ascites. RefertoUpToDatetopiconinitialtherapyofascitesin
adultswithcirrhosis.

Triamterene Triamtereneclearancedecreased. Lowerstartingdosesandlessfrequentdosing


Diureticeffectrelativelyunchangedincompensated dependingonseverityofCLD.
disease.

Nitrates MostnitratesundergononCYPhepaticand Nospecificdoseadjustmentavailable.


extrahepaticmetabolism. Doseshouldbetitratedbaseduponclinicalresponse.
Orallyadministeredisosorbidedinitrateundergoes
firstpasshepaticextractionbioavailabilitymaybe
increasedinadvancedCLDorcirrhosis.
PatientswithadvancedCLDorcirrhosismayhavea
morepronouncedresponsetonitrates,including
nitrateassociatedadverseeffects(eg,hypotension,
bradycardia).

Ranolazine RanolazineundergoescomplexhepaticCYP3Aand Useofranolazineinpatientswithcirrhosisandany


extrahepaticmetabolismconcentrationsare degreeofhepaticimpairmentiscontraindicated
significantlyelevatedinmoderatetoseverehepatic accordingtothelicensedproductinformation.
impairment.
Patientswithcirrhosis,particularlyifthereisaTIPS
orsurgicalshuntpresent,maybeatelevatedriskof
developingpotentiallyfatalventriculararrhythmiasdue
toQTprolongation.

Statins Statinsaregenerallywelltoleratedinpatientswith Initiatestatintreatmentatlowestdailydose(eg,


compensatedcirrhosisandhaveestablishedCVD pravastatin10mg)andtitrategraduallybasedupon
benefitsintreatmentofpatientswithNAFLD,viral hypolipidemicresponse.
hepatitis,andprimarybiliarycirrhosis. Whilenolongerrecommendedinthegeneral
Moststatinsaresubjecttohighfirstpassextraction population,ALTmonitoringisreasonableforstatin
and/orarehighlyboundtoplasmaproteins,which treatmentofpatientswithcirrhosis.
canincreasebloodconcentrationsinpatientswith Avoidstatinswithdecompensateddiseaseor
hepaticimpairment. significantcholestasis.
PravastatindoesnotundergoCYPmetabolismits RefertoUpToDatetopicreviewofstatinactions,side
clearanceislargelydependentuponrenalfunction. effects,andadministration.
Safetydataarereassuringamongpravastatintreated
patientswithcompensatednoncholestaticCLD.
Apronouncedhypolipidemicresponseinrelationto
dosemaybeevidenceofstatinaccumulation.

Gastrointestinal

Protonpumpinhibitors Protonpumpinhibitorsappeartobeapotentialrisk Acidsuppressivemedicationsshouldonlybegivento


factorforSBP,C.difficile,andotherseriousinfections patientswhohaveclearindicationsfortheiruse.
inpatientswithcirrhosis. RefertoUpToDatetopicsonoverviewoftheuseof
Protonpumpinhibitorsappeartobeapotentialrisk protonpumpinhibitorsforthetreatmentofacid
factorforhepaticencephalopathy. relateddisordersandontreatmentandprophylaxisof
spontaneousbacterialperitonitis.

Herbalmedicinesandsupplements

Avarietyofherbalmedicinesandsupplementsmaybe Itisimportantforthecliniciantoaskpatientswith
usedbypatientswithcirrhosis(eg,silymarin[milk CLDorcirrhosisaboutherbalmedicinesand
thistle]). supplements.
Herbsandsupplementsmaycontainundisclosed Forinformationonsilymarin(milkthistle),referto
ingredientsandcontaminants,includingprescription UpToDatetopicreviewofinvestigationaltherapiesfor
medicationsthatmaybehepatotoxicorinteractwith hepatitisCvirusinfection.
othermedications(eg,St.John'swort). AdditionalinformationisfoundinUpToDatetopic
reviewofhepatoxicityduetoherbalmedicationsand
supplements.

Hypnoticsandsedatives

Diazepam ExtensivemetabolisminliverbyCYPtoactive Noadjustmentneededforinitialdose.


metabolites. Riskofaccumulationandoversedationwithrepeated
Clearancedecreasedby50%. doses.
Halflifeofdrugandactivemetabolitesprolongedtwo Reducemaintenancedoseandfrequencybyupto
tofivefold(ie,upto500hours). 50%orconsideranothersedativeoption.
Prolongedeffectmightbeusefulforpatientsbeing
treatedforalcoholwithdrawalorseizures.
AvoidinpatientswithHE.

Lorazepam Undergoesmetabolismbyglucuronidation,whichis Generallyagoodchoicewhenbenzodiazepine


relativelypreservedinmildtomoderatehepatic treatmentindicated.
insufficiency. Nospecificdoseadjustmenttitrategraduallydueto
prolongedonset.
Withprolongeduseoruseasacontinuousinfusion
riskofdrugaccumulationandoversedation.
AvoidinpatientswithHE.

Midazolam ExtensivelymetabolizedintheliverbyCYP3A4and, Oralpreparationshouldbeavoidedinpatientswith


whenadministeredorally,undergoesfirstpasshepatic advancedCLDorcirrhosisduetounpredictable
extraction. bioavailability.
Halflifeofdrugandactivemetaboliteareincreasedin ForIVuse,nospecificdoseadjustmentonce
hepaticimpairment. adequatelysedatedusingsmallincrementaldoses,a
reducedmaintenancedoseandfrequencymaybe
neededtoavoidaccumulationandoversedationof
patientswithadvancedCLDorcirrhosis.
AvoidinpatientswithHE.

Zolpidem Halflifeprolongedtwofoldinmoderatehepatic Uselowestpossibledoseinpatientswithmildto


impairmentandfourfoldormoreinadvancedCLD. moderatehepaticimpairment.
Immediatereleasepreparationmaybebrokento
provide2.5mgdose.
AvoiduseinadvancedCLDmayprecipitateorworsen
HE.

Opioidusedisorder(opioidaddiction)treatment

Buprenorphinenaloxone Buccallyandsublinguallyadministerednaloxone, Buprenorphinenaloxonecombinationisnot


whichisincludedinthiscombinationtodeterabuse recommendedinpatientswithadvancedCLDor
(ie,crushing,snorting,injecting),issystemically cirrhosisduetoincreasedbioavailabilityofnaloxone.
absorbedinpatientswithmoderatetoseverehepatic
impairment.
Absorptionofnaloxonecanreverseeffectof
buprenorphineandprecipitateanopioidwithdrawal
syndrome.

Thisisnotacompletelistofcautionaryinformationanddoseadjustmentsforuseofmedicationsbypatientswithhepaticimpairment.Referto
theLexicompindividualdrugmonographsincludedwithUpToDateforadditionalinformation.Patientswithcirrhosisseemtobeatincreasedrisk
ofadverseoutcomesduetodrugdruginteractionsanddrugsthatcauseQTcprolongation,particularlyinthesettingofadvancedor
decompensateddiseaseandinthosewhohaveundergoneTIPSorsurgicalshunts.RefertotopiconacquiredlongQTsyndromefordetails.
SeparatecalculatorsareavailableinUpToDatefordeterminationofChildPughclassificationforseverityofcirrhosisbaseduponpatientclinical
andlaboratorydata(conventionalorSIunits).
Mostdrugsusedinthetreatmentoffrequentlyencounteredchronicdiseasesandinfectionscanbeusedsafelyinpatientswithchronicliver
diseaseorcompensatedcirrhosis.
Often,areduceddose,frequencyofadministration,oravoidanceofcertainmedicationsisrecommendedinthesettingofadvancedCLDor
cirrhosisbaseduponchangesindrugdisposition(eg,increasedoralbioavailability,decreasedmetabolismorproteinbinding),alteredtoxicity,
orduetoriskofprecipitatingcirrhosisassociatedcomplications(ie,avoidanceofdrugsorregimensthatcancauseGIbleeding,SBP,HE,or
renalfailure).

CLD:chronicliverdiseaseCrcl:creatinineclearanceCVD:cardiovasculardiseaseCYP:cytochromeP450DILI:druginducedliverinjuryGI:
gastrointestinalHE:hepaticencephalopathyNAFLD:nonalcoholicfattyliverdiseaseSBP:spontaneousbacterialperitonitisTIPS:transjugular
intrahepaticportosystemicshuntsVd:volumeofdistributionPK:pharmacokineticsUGT:uridine5'diphosphoglucuronosyltransferasehepatic
metabolism.
*RefertoUpToDatetopicreviewofmanagementofpaininpatientswithcirrhosisincludingaseparatetableonanalgesicsuseinadultpatientswith
advancedchronicliverdiseaseorcirrhosis.
NOTE:ThefollowingareantibioticsandantifungalsnotlistedinthetableabovethatshouldbeusedwithcautioninadvancedCLDorcirrhosis:
chloramphenicol,griseofulvin,nalidixicacid,nitrofurantoin(chronicuse),andtelithromycin.

Preparedwithdatafrom:
1.LewisJH,StineJG.Reviewarticle:Prescribingmedicationsinpatientswithcirrhosisapracticalguide.AlimentPharmacolTher201337:1132.
2.VerbeeckRK.Pharmacokineticsanddosageadjustmentinpatientswithhepaticdysfunction.EurJClinPharmacol200864:1147.
3.KlotzU.Antiarrhythmics:eliminationanddosageconsiderationsinhepaticimpairment.ClinPharmacokinet200746:985.
4.CalderonRM,CubedduLX,GoldbergRB,SchiffER.Statinsinthetreatmentofdyslipidemiainthepresenceofelevatedliveraminotransferase
levels:atherapeuticdilemma.MayoClinProc201085:349.
5.MauriCM,FiorentiniSP,AltamuraAC.Pharmacokineticsofantidepressantsinpatientswithhepaticimpairment.ClinPharmacokinet2014
53:1069.
6.TsaiCF,ChenMH,WangYP,etal.Protonpumpinhibitorsincreaseriskforhepaticencephalopathyinpatientswithcirrhosisinapopulation
study.Gastroenterology2017152:134.

Graphic90194Version9.0
Analgesicuseinadultpatientswithadvancedchronicliverdiseaseorcirrhosis

Alteredresponseandpharmacokinetics Managementsuggestions

Nonopioidanalgesics

Acetaminophen Glutathionetissuestoresneededtoblockformationof Acetaminophenisgenerallywelltoleratedinpatients


(paracetamol) acetaminophen'stoxicmetabolite(NAPQI)arereduced withCLDorcirrhosiswhodonotconsumealcohol,
inindividualswithcirrhosisormalnutrition,thereby providedthetotaldailydoseislimitedtonomore
loweringthedosethresholdofacetaminophenthat than2g/day.
canbesafelyadministeredeachday. Forshorttermoronetimeuse,amaximumtotal
Activealcoholconsumptionfurtherreducesavailable acetaminophendoseofupto3g/daymaybe
glutathionestores. consideredinlowerriskpatients(eg,donotconsume
Halflifeofacetaminophenmaybeprolongedbyupto alcohol)withCLDorearlystagecompensated
twofoldcomparedwithhealthypatients. cirrhosis.
Warnpatientsconcerningacetaminophencontentin
combinationprescriptionanalgesics(eg,oxycodone
acetaminophen)andnonprescription(OTC)
preparations.
AvoiduseinpatientswithadvancedCLDorcirrhosis
whoareactivelyconsumingalcohol,malnourished,
noteating,receivingmultiplemedicationsthat
undergohepaticbiotransformations,oranyco
administeredmedicationthatisapotentinducerof
hepaticenzymes.
Alistofmedicationsthatinducehepaticenzymesis
providedinaseparatetable.

Nonselective NSAIDscandecreaseGFRandimpairrenalfunctionin NSAIDsandaspirinshouldbeavoidedinpatientswith


nonsteroidalanti patientswithadvancedCLDorcirrhosis. advancedCLDorcirrhosis.
inflammatorydrugs MostNSAIDsaremetabolizedbyCYPandhighly Lowdoseacetaminophenshouldbeusedinsteadof
(NSAIDs)including boundtoserumalbumin,increasingdrug NSAIDs.
aspirin bioavailabilityandpotentialfortoxicityinpatientswith
advancedCLDorcirrhosis.
AnincreasedriskofGImucosalbleeding,variceal
hemorrhage,impairedrenalfunction,anddevelopment
ofdiureticresistantascitesisseenwithuseofNSAIDs
inpatientswithcirrhosiswithportalhypertension.
IndividualNSAIDs(eg,diclofenac)havebeen
associatedwithhepatotoxicityingeneralpopulation.

SelectiveCOX2 Availabledataareinadequatetoestablishthesafetyof WeadviseagainstuseofselectiveCOX2inhibitorsin


inhibitors selectiveCOX2inhibitorsinpatientswithadvanced patientswithadvancedCLDorcirrhosis,pending
CLDorcirrhosis.Seetextfordetail. availabilityofadditionalsafetydata.
Excesscardiovasculareventshavebeenobservedwith Ifused,celecoxibproductinformationsuggestsa
thisclassofmedicationswhenusedbypatients 50%dosereductionforChildPughclassBcirrhosis.
withoutcirrhosis.

Opioidanalgesics(seeimportantnote)*

Fentanyl MetabolizedbyCYP3A4toinactive(nontoxic) GenerallyagoodchoiceforpatientswithCLDor


metabolites. cirrhosiswhenopiatetreatmentindicated.
Parentdrugcanaccumulateafterrepeateddosingor Usefuloptioninpatientswithrenalfailureinsettingof
whenadministeredasacontinuousinfusiondueto cirrhosis.
tissueandproteinbinding. Nodoseadjustmentneededforsingledose.
Lesshistaminereleasethanotheropiates. Withrepeateddosing,reducedoseandfrequencyby
Lesshemodynamicdisturbancethanotheropiates. approximately25to50%.
Initiatetransdermalpatchathalfusualdose.

Hydrocodone, MetabolizedtoactivemetabolitebyCYP2D6and3A4 Duetovariabilityofonsetandanalgesicefficacyin


oxycodone whichmayresultinaprolongedtimetoonset, hepaticinsufficiency,fentanylorhydromorphonemay
variableanalgesicefficacy,andriskofaccumulationin bebettertoleratedandmoresafelyandpredictably
patientswithadvancedCLDorcirrhosis. adjustedthanhydrocodoneandoxycodoneinpatients
withadvancedCLDorcirrhosis.
Ifused,reducedoseandfrequency.

Hydromorphone HepaticallymetabolizedbynonCYPtransformations Generallyagoodchoiceforpatientswithadvanced


(glucuronidation)toapparentlyinactivemetabolites. CLDorcirrhosis.
OralbioavailabilityinadvancedCLDorcirrhosisseems Reducedoseandfrequencybyapproximately50%.
tobeincreasedrelativetohealthyindividualsdueto Titratedosegraduallytoavoidaccumulationofactive
diminishedfirstpassextraction,butspecificdataare drug.
lacking,andwideinterindividualvariabilityis Usefuloptioninpatientswithrenalfailureinsettingof
observed. cirrhosis.
SmallvolumeforIVpreparationandnonCYP3A4
metabolismmaybeadvantageousgivenclinical
setting.

Meperidine(pethidine), Alteredoralbioavailabilityandelevatedriskof Meperidineandcodeineshouldbeavoidedinpatients


codeine accumulationofintermediates(codeine)ortoxic withadvancedCLDorcirrhosis.
metabolite(meperidine).
Meperidineishighlyboundtoserumprotein.
Unpredictableanalgesicefficacyandincreasedriskof
toxicityinpatientswithadvancedCLDorcirrhosis.

Morphine OralbioavailabilityinadvancedCLDorcirrhosis Reducedoseandfrequencybyapproximately50%in


increasedupto100%relativetohealthyindividuals advancedCLDorcirrhosis.
duetodiminishedfirstpassextraction.Wideinter Titratedosegraduallytoavoidaccumulationofactive
individualvariabilitymaybeseen. drug.
HepaticallymetabolizedbynonCYPtransformations Avoidinpatientswithcirrhosisandrenalfailure.
(glucuronidation).
Halflifecanbeincreasedbyuptotwofold.
Accumulationofmetaboliteswithcomplexeffects(eg,
respiratorydepression,analgesictolerance,
neurotoxicity)canoccurinpatientswithcirrhosisand
renalfailure.

Naloxonecontaining Orallyadministerednaloxone,whichisincludedin Oxycodonenaloxone:


opioidcombinations thesecombinationstodeterabuse(ie,crushing, Reducestartingdosebyonehalftotwothirdsin
snorting)andcounteractconstipationbyalocal mildhepaticimpairment
effect,issystemicallyabsorbedinpatients UseinadvancedCLDorcirrhosisis
withmoderatetoseverehepaticimpairment. contraindicated
Systemicabsorptionofnaloxonewillreverseanalgesic Pentazocinenaloxone:Avoiduse
efficacyandcanprecipitateopioidwithdrawal.

Remifentanil Clearedbynonspecificplasmaesterasestoinactive Noadjustmentneeded.


metabolites.
Doesnotaccumulateinhepaticorrenalinsufficiency.
Promptreversalofanalgesiaandsedationupon
discontinuation.

Tramadol Hepaticallymetabolizedtoactivemetaboliteby Avoiduseinpatientswithdecompensatedcirrhosis.


CYP3A4,2D6andglucuronidation. Avoiduseinpatientsatriskforseizures.
Unpredictableonset,variableanalgesicefficacy,and Baseduponlimitedexperience,areduceddoseof25
riskofaccumulationinpatientswithcirrhosis. mgeveryeighthoursmaybeconsideredfortreatment
Caninteractwithserotoninergicmedicationsincluding ofpaininpatientswithadvancedCLDorwell
antidepressants. compensatedcirrhosis.

Adjunctiveagentsforneuropathicpain

Carbamazepine Carbamazepineisapotentinducerofhepaticenzymes Carbamazepineshouldbeavoidedastherearesafer


andhasbeenassociatedwithhepatotoxicityand optionsfortreatmentofneuropathicpaininpatients
seriousallergicreactionsingeneticallypredisposed withadvancedCLDorcirrhosis.
individuals.
Mayprecipitaterapiddecompensationinpatientswith
cirrhosis.

Gabapentin Nothepaticallymetabolizedorboundtoplasma Initiatetreatmentat300mgorallyperdayand


proteins. graduallytitratedoseifneededoverweeksdueto
Highlydependentuponrenalfunctionforclearanceof delayedonsetofactionandtoimprovetolerability.
unchangeddrug. Maintenancedoseisdependentuponrenalfunction.
Sedation,ataxia,dizziness,andnauseamaylimit Forspecificadjustment,refertoLexicompmonograph
usefulnessinpatientswithadvancedCLDorcirrhosis. includedwithUpToDate.
Accordingtotheproductinformation,shouldnotbe
abruptlystoppedduetoriskofdiscontinuation
symptoms(eg,nausea,insomnia,anxiety)and/or
reboundseizuresinatriskpatients.

Lidocainetopicalpatch Low(3to5%)systemicabsorptionthroughintact Agoodchoiceforlocalreliefofpaininlimitedareas


skin. ofintactskininpatientswithadvancedCLDor
cirrhosis.
Noadjustmentneededinhepaticimpairment.

Nortriptyline Subjecttoextensivefirstpassmetabolismand Initiatetreatmentat10mgorallyeachnightand


CYP2D6transformations,whichincludeactiveand graduallytitratedoseifneededoverweeksdueto
inactivemetabolites. delayedonsetofactionandtoimprovetolerability.
Accumulationofmetabolitesinhepaticimpairmentis Use"low"maintenancedoseforneuropathicpain(eg,
lesslikelywithnortriptylinethanamitriptyline. 25mgtonomorethan50mgdaily)todecreaserisk
Doserelatedanticholinergicandcardiovascularside ofaccumulation.
effectsmaybepoorlytoleratedinmedicallyillpatients
withadvancedCLDorcirrhosis.

Pregabalin Nothepaticallymetabolizedorboundtoplasma Initiatetreatmentat50mgorallytwiceperdayand


proteins. graduallytitratedoseifneededoverweeksdueto
Highlydependentuponrenalfunctionforclearanceof delayedonsetofaction.
unchangeddrug. Maintenancedoseisdependentuponrenalfunction.
Sedationanddizzinessmaylimitusefulnessinpatients Forspecificadjustment,refertoLexicompmonograph
withadvancedCLDorcirrhosis. includedwithUpToDate.
Accordingtotheproductinformation,shouldnotbe
abruptlystoppedduetoriskofdiscontinuation
symptoms(eg,nausea,insomnia,anxiety)and/or
reboundseizuresinatriskpatients.
Forinformationaboutuseandadjustmentofmedicationsotherthananalgesicsinchronicliverdisease,refertoseparatetableinUpToDateon
nonanalgesicmedicationsusedinadultpatientswithadvancedchronicliverdiseaseorcirrhosis.

OTC:overthecounteranalgesicCOX2:cyclooxygenase2CLD:chronicliverdiseaseCYP:cytochromeP450NSAID:nonsteroidalantiinflammatory
drugNAPQI:nacetylpbenzoquinoneimineHE:hepaticencephalopathy.
*NOTE:AllopioidscanworsenorprecipitateHEandshouldbeusedcautiouslyoravoidedinpatientswithportalhypertensionandpreexistingHE.

Preparedwithdatafrom:
1.LewisJH,StineJG.Reviewarticle:Prescribingmedicationsinpatientswithcirrhosisapracticalguide.AlimentPharmacolTher201337:1132.
2.ChandokN,WattKD.Painmanagementinthecirrhoticpatient:Theclinicalchallenge.MayoClinProc201085(5):451.

Graphic90196Version11.0
VaccinesthatmightbeindicatedforadultsbasedonmedicalandotherindicationsUnitedStates,2017

*Influenzavaccination:
Generalinformation
Allpersonsaged6monthsorolderwhodonothaveacontraindicationshouldreceiveannualinfluenzavaccinationwithanageappropriateformulationofina
recombinantinfluenzavaccine(RIV).
InadditiontostandarddoseIIV,availableoptionsforadultsinspecificagegroupsincludehighdoseoradjuvantedIIVforadultsaged65yearsorolder,int
64years,andRIVforadultsaged18yearsorolder.
Notes:Liveattenuatedinfluenzavaccine(LAIV)shouldnotbeusedduringthe2016to2017influenzaseason.Alistofcurrentlyavailableinfluenzavaccinesis
www.cdc.gov/flu/protect/vaccine/vaccines.htm.
Specialpopulations
AdultswithahistoryofeggallergywhohaveonlyhivesafterexposuretoeggshouldreceiveageappropriateIIVorRIV.
Adultswithahistoryofeggallergyotherthanhives(eg,angioedema,respiratorydistress,lightheadedness,orrecurrentemesis)orwhorequiredepinephrine
interventionmayreceiveageappropriateIIVorRIV.Theselectedvaccineshouldbeadministeredinaninpatientoroutpatientmedicalsettingandunderthes
abletorecognizeandmanagesevereallergicconditions.
PregnantwomenandwomenwhomightbecomepregnantintheupcominginfluenzaseasonshouldreceiveIIV.
Tetanus,diphtheria,andacellularpertussisvaccination:
Generalinformation
Adultswhohavenotreceivedtetanusanddiphtheriatoxoidsandacellularpertussisvaccine(Tdap)orforwhompertussisvaccinationstatusisunknownshou
tetanusanddiphtheriatoxoids(Td)boosterevery10years.Tdapshouldbeadministeredregardlessofwhenatetanusordiphtheriatoxoidcontainingvaccine
Adultswithanunknownorincompletehistoryofa3doseprimaryserieswithtetanusanddiphtheriatoxoidcontainingvaccinesshouldcompletetheprimary
Unvaccinatedadultsshouldreceivethefirst2dosesatleast4weeksapartandthethirddose6to12monthsaftertheseconddose.
Notes:InformationontheuseofTdorTdapastetanusprophylaxisinwoundmanagementisavailableatwww.cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.h
Specialpopulations
Pregnantwomenshouldreceive1doseofTdapduringeachpregnancy,preferablyduringtheearlypartofgestationalweeks27to36,regardlessofpriorhist
Measles,mumps,andrubellavaccination:
Generalinformation
Adultsbornin1957orlaterwithoutacceptableevidenceofimmunitytomeasles,mumps,orrubella(definedbelow)shouldreceive1doseofmeasles,mumps
haveamedicalcontraindicationtothevaccine(eg,pregnancyorsevereimmunodeficiency).
Notes:Acceptableevidenceofimmunitytomeasles,mumps,orrubellainadultsisbornbefore1957,documentationofreceiptofMMR,orlaboratoryevidence
ofhealthcareproviderdiagnoseddiseasewithoutlaboratoryconfirmationisnotacceptableevidenceofimmunity.
Specialpopulations
Pregnantwomenwhodonothaveevidenceofimmunitytorubellashouldreceive1doseofMMRuponcompletionorterminationofpregnancyandbeforedisc
pregnantwomenofchildbearingagewithoutevidenceofrubellaimmunityshouldreceive1doseofMMR.
Adultswithprimaryoracquiredimmunodeficiencyincludingmalignantconditionsaffectingthebonemarroworlymphaticsystem,systemicimmunosuppressiv
shouldnotreceiveMMR.
Adultswithhumanimmunodeficiencyvirus(HIV)infectionandCD4+Tlymphocytecount200cells/mcLforatleast6monthswhodonothaveevidenceofm
shouldreceive2dosesofMMRatleast28daysapart.AdultswithHIVinfectionandCD4+Tlymphocytecount<200cells/mcLshouldnotreceiveMMR.
Adultswhoworkinhealthcarefacilitiesshouldreceive2dosesofMMRatleast28daysaparthealthcarepersonnelbornbefore1957whoareunvaccinatedor
mumps,orrubellaimmunity,orlaboratoryconfirmationofdiseaseshouldbeconsideredforvaccinationwith2dosesofMMRatleast28daysapartformeasle
rubella.
Adultswhoarestudentsinpostsecondaryeducationalinstitutionsorplantotravelinternationallyshouldreceive2dosesofMMRatleast28daysapart.
Adultswhoreceivedinactivated(killed)measlesvaccineormeaslesvaccineofunknowntypeduringyears1963to1967shouldberevaccinatedwith1or2do
Adultswhowerevaccinatedbefore1979witheitherinactivatedmumpsvaccineormumpsvaccineofunknowntypewhoareathighriskformumpsinfection,
beconsideredforrevaccinationwith2dosesofMMRatleast28daysapart.
Varicellavaccination:
Generalinformation
Adultswithoutevidenceofimmunitytovaricella(definedbelow)shouldreceive2dosesofsingleantigenvaricellavaccine(VAR)4to8weeksapart,oraseco
PersonswithoutevidenceofimmunityforwhomVARshouldbeemphasizedareadultswhohaveclosecontactwithpersonsathighriskforseriouscomplicati
householdcontactsofimmunocompromisedpersons),adultswholiveorworkinanenvironmentinwhichtransmissionofvaricellazostervirusislikely(eg,t
andstaffininstitutionalsettings),adultswholiveorworkinenvironmentsinwhichvaricellatransmissionhasbeenreported(eg,collegestudents,residentsa
institutions,andmilitarypersonnel),nonpregnantwomenofchildbearingage,adolescentsandadultslivinginhouseholdswithchildren,andinternationaltra
Notes:EvidenceofimmunitytovaricellainadultsisUnitedStatesbornbefore1980(forpregnantwomenandhealthcarepersonnel,UnitedStatesbornbefore
immunity),documentationof2dosesofVARatleast4weeksapart,historyofvaricellaorherpeszosterdiagnosisorverificationofvaricellaorherpeszoster
laboratoryevidenceofimmunityordisease.
Specialpopulations
Pregnantwomenshouldbeassessedforevidenceofvaricellaimmunity.Pregnantwomenwhodonothaveevidenceofimmunityshouldreceivethefirstdose
pregnancyandbeforedischargefromthehealthcarefacility,andtheseconddose4to8weeksafterthefirstdose.
Healthcareinstitutionsshouldassessandensurethatallhealthcarepersonnelhaveevidenceofimmunitytovaricella.
Adultswithmalignantconditions,includingthosethataffectthebonemarroworlymphaticsystemorwhoreceivesystemicimmunosuppressivetherapy,shou
Adultswithhumanimmunodeficiencyvirus(HIV)infectionandCD4+Tlymphocytecount200cells/mcLmayreceive2dosesofVAR3monthsapart.Adults
lymphocytecount<200cells/mcLshouldnotreceiveVAR.
Herpeszostervaccination:
Generalinformation
Adultsaged60yearsoroldershouldreceive1doseofherpeszostervaccine(HZV),regardlessofwhethertheyhadapriorepisodeofherpeszoster.
Specialpopulations
Adultsaged60yearsorolderwithchronicmedicalconditionsmayreceiveHZVunlesstheyhaveamedicalcontraindication(eg,pregnancyorsevereimmunod
Adultswithmalignantconditions,includingthosethataffectthebonemarroworlymphaticsystemorwhoreceivesystemicimmunosuppressivetherapy,shou
AdultswithhumanimmunodeficiencyvirusinfectionandCD4+Tlymphocytecount<200cells/mcLshouldnotreceiveHZV.
Humanpapillomavirusvaccination:
Generalinformation
Adultfemalesthroughage26yearsandadultmalesthroughage21yearswhohavenotreceivedanyhumanpapillomavirus(HPV)vaccineshouldreceivea3d
and6months.Malesaged22through26yearsmaybevaccinatedwitha3doseseriesofHPVvaccineat0,1to2,and6months.
Adultfemalesthroughage26yearsandadultmalesthroughage21years(andmalesaged22through26yearswhomayreceiveHPVvaccination)whoinitiate
15yearsandreceived2dosesatleast5monthsapartareconsideredadequatelyvaccinatedanddonotneedanadditionaldoseofHPVvaccine.
Adultfemalesthroughage26yearsandadultmalesthroughage21years(andmalesaged22through26yearswhomayreceiveHPVvaccination)whoinitiate
15yearsandreceivedonly1dose,or2doseslessthan5monthsapart,arenotconsideredadequatelyvaccinatedandshouldreceive1additionaldoseofHPV
Notes:HPVvaccinationisroutinelyrecommendedforchildrenatage11or12years.ForadultswhohadinitiatedbutdidnotcompletetheHPVvaccinationser
vaccination(describedabove)andotherfactors(describedbelow)todetermineiftheyhavebeenadequatelyvaccinated.
Specialpopulations
Menwhohavesexwithmenthroughage26yearswhohavenotreceivedanyHPVvaccineshouldreceivea3doseseriesofHPVvaccineat0,1to2,and6m
Adultfemalesandmalesthroughage26yearswithimmunocompromisingconditions(describedbelow),includingthosewithhumanimmunodeficiencyvirusi
HPVvaccineat0,1to2,and6months.
PregnantwomenarenotrecommendedtoreceiveHPVvaccine,althoughthereisnoevidencethatthevaccineposesharm.Ifawomanisfoundtobepregnan
delaytheremainingdosesuntilafterthepregnancy.Nootherinterventionisneeded.PregnancytestingisnotneededbeforeadministeringHPVvaccine.
Notes:Immunocompromisingconditionsforwhicha3doseseriesofHPVvaccineisindicatedareprimaryorsecondaryimmunocompromisingconditionstha
immunity(eg,Blymphocyteantibodydeficiencies,completeorpartialTlymphocytedefects,HIVinfection,malignantneoplasm,transplantation,autoimmuned
Pneumococcalvaccination:
Generalinformation
Adultswhoareimmunocompetentandaged65yearsoroldershouldreceive13valentpneumococcalconjugatevaccine(PCV13)followedby23valentpneum
atleast1yearafterPCV13.
Notes:Adultsarerecommendedtoreceive1doseofPCV13and1,2,or3dosesofPPSV23dependingonindication.WhenbothPCV13andPPSV23areindic
PCV13andPPSV23shouldnotbeadministeredduringthesamevisit.IfPPSV23haspreviouslybeenadministered,PCV13shouldbeadministeredatleast1ye
dosesofPPSV23areindicated,theintervalbetweenPPSV23dosesshouldbeatleast5years.Supplementalinformationonpneumococcalvaccinetimingfora
aged19yearsorolderathighriskforpneumococcaldisease(describedbelow)isavailableathttps://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo
ofPPSV23areindicatedforadultswhoreceivedPPSV23atage65yearsorolder.Whenindicated,PCV13andPPSV23shouldbeadministeredtoadultswhose
incompleteorunknown.
Specialpopulations
Adultsaged19through64yearswithchronicheartdiseaseincludingcongestiveheartfailureandcardiomyopathies(excludinghypertension)chroniclungdi
disease,emphysema,andasthmachronicliverdiseaseincludingcirrhosisalcoholismordiabetesmellitusorwhosmokecigarettesshouldreceivePPSV23.
receivePCV13andanotherdoseofPPSV23atleast1yearafterPCV13andatleast5yearsafterthemostrecentdoseofPPSV23.
Adultsaged19yearsorolderwithimmunocompromisingconditionsoranatomicalorfunctionalasplenia(describedbelow)shouldreceivePCV13andadose
followedbyaseconddoseofPPSV23atleast5yearsafterthefirstdoseofPPSV23.IfthemostrecentdoseofPPSV23wasadministeredbeforeage65years
anotherdoseofPPSV23atleast8weeksafterPCV13andatleast5yearsafterthemostrecentdoseofPPSV23.
Adultsaged19yearsorolderwithcerebrospinalfluidleakorcochlearimplantshouldreceivePCV13followedbyPPSV23atleast8weeksafterPCV13.Ifthem
administeredbeforeage65years,atage65yearsorolder,administeranotherdoseofPPSV23atleast8weeksafterPCV13andatleast5yearsafterthemos
Notes:ImmunocompromisingconditionsthatareindicationsforpneumococcalvaccinationarecongenitaloracquiredimmunodeficiencyincludingBorTlym
deficiencies,andphagocyticdisordersexcludingchronicgranulomatousdiseasehumanimmunodeficiencyvirusinfectionchronicrenalfailureandnephrotic
disease,generalizedmalignancy,andmultiplemyelomasolidorgantransplantandiatrogenicimmunosuppressionincludinglongtermsystemiccorticosteroid
functionalaspleniathatareindicationsforpneumococcalvaccinationaresicklecelldiseaseandotherhemoglobinopathies,congenitaloracquiredasplenia,spl
Pneumococcalvaccinesshouldbegivenatleast2weeksbeforeimmunosuppressivetherapyoranelectivesplenectomy,andassoonaspossibletoadultswho
HepatitisAvaccination:
Generalinformation
AdultswhoseekprotectionfromhepatitisAvirusinfectionmayreceivea2doseseriesofsingleantigenhepatitisAvaccine(HepA)ateither0and6to12mon
(Vaqta).AdultsmayalsoreceiveacombinedhepatitisAandhepatitisBvaccine(HepAHepBTwinrix)asa3doseseriesat0,1,and6months.Acknowledgme
seekprotectionisnotneeded.
Specialpopulations
AdultswithanyofthefollowingindicationsshouldreceiveaHepAseries:havechronicliverdisease,receiveclottingfactorconcentrates,menwhohavesexw
drugs,orworkwithhepatitisAvirusinfectedprimatesorinahepatitisAresearchlaboratorysetting.
AdultswhotravelincountrieswithhighorintermediatelevelsofendemichepatitisAinfectionoranticipateclosepersonalcontactwithaninternationaladopte
regularlybabysit)fromacountrywithhighorintermediatelevelofendemichepatitisAinfectionwithinthefirst60daysofarrivalintheUnitedStatesshouldr
**HepatitisBvaccination:
Generalinformation
AdultswhoseekprotectionfromhepatitisBvirusinfectionmayreceivea3doseseriesofsingleantigenhepatitisBvaccine(HepBEngerixB,RecombivaxHB)
receiveacombinedhepatitisAandhepatitisBvaccine(HepAHepBTwinrix)at0,1,and6months.Acknowledgmentofaspecificriskfactorbythosewhosee
Specialpopulations
AdultsatriskforhepatitisBvirusinfectionbysexualexposureshouldreceiveaHepBseries,includingsexpartnersofhepatitisBsurfaceantigen(HBsAg)pos
arenotinamutuallymonogamousrelationship,personsseekingevaluationortreatmentforasexuallytransmittedinfection,andmenwhohavesexwithmen
AdultsatriskforhepatitisBvirusinfectionbypercutaneousormucosalexposuretobloodshouldreceiveaHepBseries,includingadultswhoarerecentorcu
contactsofHBsAgpositivepersons,residentsandstaffoffacilitiesfordevelopmentallydisabledpersons,incarcerated,healthcareandpublicsafetyworkersat
contaminatedbodyfluids,youngerthanage60yearswithdiabetesmellitus,andage60yearsorolderwithdiabetesmellitusatthediscretionofthetreatingc
Adultswithchronicliverdiseaseincluding,butnotlimitedto,hepatitisCvirusinfection,cirrhosis,fattyliverdisease,alcoholicliverdisease,autoimmunehepa
(ALT)oraspartateaminotransferase(AST)levelgreaterthantwicetheupperlimitofnormalshouldreceiveaHepBseries.
Adultswithendstagerenaldiseaseincludingthoseonpredialysiscare,hemodialysis,peritonealdialysis,andhomedialysisshouldreceiveaHepBseries.Adu
doseseriesof40mcgRecombivaxHBat0,1,and6monthsora4doseseriesof40mcgEngerixBat0,1,2,and6months.
AdultswithhumanimmunodeficiencyvirusinfectionshouldreceiveaHepBseries.
PregnantwomenwhoareatriskforhepatitisBvirusinfectionduringpregnancy(eg,havingmorethanonesexpartnerduringtheprevioussixmonths,been
transmittedinfection,recentorcurrentinjectiondruguse,orhadanHBsAgpositivesexpartner)shouldreceiveaHepBseries.
InternationaltravelerstoregionswithhighorintermediatelevelsofendemichepatitisBvirusinfectionshouldreceiveaHepBseries.
AdultsinthefollowingsettingsareassumedtobeatriskforhepatitisBvirusinfectionandshouldreceiveaHepBseries:sexuallytransmitteddiseasetreatmen
facilities,facilitiesprovidingdrugabusetreatmentandpreventionservices,healthcaresettingstargetingservicestopersonswhoinjectdrugs,correctionalfac
servicestoMSM,hemodialysisfacilitiesandendstagerenaldiseaseprograms,andinstitutionsandnonresidentialdaycarefacilitiesfordevelopmentallydisabl
Meningococcalvaccination:
Specialpopulations
Adultswithanatomicalorfunctionalaspleniaorpersistentcomplementcomponentdeficienciesshouldreceivea2doseprimaryseriesofserogroupsA,C,W,
(MenACWY)atleast2monthsapartandrevaccinateevery5years.TheyshouldalsoreceiveaseriesofserogroupBmeningococcalvaccine(MenB)witheither
least1monthapartora3doseseriesofMenBFHbp(Trumenba)at0,1to2,and6months.
Adultswithhumanimmunodeficiencyvirusinfectionwhohavenotbeenpreviouslyvaccinatedshouldreceivea2doseprimaryseriesofMenACWYatleast2m
Thosewhopreviouslyreceived1doseofMenACWYshouldreceiveaseconddoseatleast2monthsafterthefirstdose.AdultswithHIVinfectionarenotrouti
becausemeningococcaldiseaseinthispopulationiscausedprimarilybyserogroupsC,W,andY.
MicrobiologistswhoareroutinelyexposedtoisolatesofNeisseriameningitidisshouldreceive1doseofMenACWYandrevaccinateevery5yearsiftheriskfor
seriesofMenB4Catleast1monthapartora3doseseriesofMenBFHbpat0,1to2,and6months.
Adultsatriskbecauseofameningococcaldiseaseoutbreakshouldreceive1doseofMenACWYiftheoutbreakisattributabletoserogroupA,C,W,orY,orei
monthapartora3doseseriesofMenBFHbpat0,1to2,and6monthsiftheoutbreakisattributabletoserogroupB.
Adultswhotraveltoorliveincountrieswithhyperendemicorepidemicmeningococcaldiseaseshouldreceive1doseofMenACWYandrevaccinateevery5yea
isnotroutinelyindicatedbecausemeningococcaldiseaseinthesecountriesisgenerallynotcausedbyserogroupB.
Militaryrecruitsshouldreceive1doseofMenACWYandrevaccinateevery5yearsiftheincreasedriskforinfectionremains.
Firstyearcollegestudentsaged21yearsoryoungerwholiveinresidencehallsshouldreceive1doseofMenACWYiftheyhavenotreceivedMenACWYatage
Youngadultsaged16through23years(preferredagerangeis16through18years)whoarehealthyandnotatincreasedriskforserogroupBmeningococc
eithera2doseseriesofMenB4Catleast1monthapartora2doseseriesofMenBFHbpat0and6monthsforshorttermprotectionagainstmoststrainso
Foradultsaged56yearsorolderwhohavenotpreviouslyreceivedserogroupsA,C,W,andYmeningococcalvaccineandneedonly1dose,meningococcalp
vaccine(MPSV4)ispreferred.ForadultswhopreviouslyreceivedMenACWYoranticipatereceivingmultipledosesofserogroupsA,C,W,andYmeningococca
Notes:MenB4CandMenBFHbparenotinterchangeable(ie,thesamevaccineshouldbeusedforalldosestocompletetheseries).Thereisnorecommendati
MenBmaybeadministeredatthesametimeasMenACWYbutatadifferentanatomicsite,iffeasible.
Haemophilusinfluenzaetypebvaccination:
Specialpopulations
Adultswhohaveanatomicalorfunctionalaspleniaorsicklecelldisease,orareundergoingelectivesplenectomyshouldreceive1doseofH.influenzae
previouslyreceivedHib.Hibshouldbeadministeredatleast14daysbeforesplenectomy.
Adultswithahematopoieticstemcelltransplant(HSCT)shouldreceive3dosesofHibinatleast4weekintervals6to12monthsaftertransplantregardlesso
Notes:HibisnotroutinelyrecommendedforadultswithhumanimmunodeficiencyvirusinfectionbecausetheirriskforHaemophilusinfluenzaetypebinfectio

Reproducedfrom:AdvisoryCommitteeonImmunizationPractices(ACIP).AdvisoryCommitteeonImmunizationPracticesRecommendedImmunizationSchedulefor
States,2017.Availableat:http://www.cdc.gov/vaccines/schedules/downloads/adult/adultcombinedschedule.pdf(AccessedonFebruary8,2017).

Graphic62130Version14.0
Precipitantsofhepaticencephalopathyinpatientswithcirrhosis

Drugs
Benzodiazepines

Nonbenzodiazepinehypnotics(eg,zolpidem)

Narcotics

Alcohol

Increasedammoniaproduction,absorptionorentryintothebrain
Excessdietaryintakeofprotein

Gastrointestinalbleeding

Infection

Electrolytedisturbancessuchashypokalemia

Constipation

Metabolicalkalosis

Dehydration
Vomiting

Diarrhea

Hemorrhage

Diuretics

Largevolumeparacentesis

Portosystemicshunting
Radiographicorsurgicallyplacedshunts

Spontaneousshunts

Vascularocclusion
Hepaticveinthrombosis

Portalveinthrombosis

Primaryhepatocellularcarcinoma

Graphic50440Version4.0
ChildPughclassificationofseverityofcirrhosis

Pointsassigned
Parameter
1 2 3

Ascites Absent Slight Moderate

Bilirubin <2mg/dL(<34.2micromol/L) 2to3mg/dL(34.2to51.3 >3mg/dL(>51.3micromol/L)


micromol/L)

Albumin >3.5g/dL(35g/L) 2.8to3.5g/dL(28to35g/L) <2.8g/dL(<28g/L)

Prothrombintime

Secondsovercontrol <4 4to6 >6

INR <1.7 1.7to2.3 >2.3

Encephalopathy None Grade1to2 Grade3to4

ModifiedChildPughclassificationoftheseverityofliverdiseaseaccordingtothedegreeofascites,theserumconcentrationsofbilirubinand
albumin,theprothrombintime,andthedegreeofencephalopathy.AtotalChildTurcottePughscoreof5to6isconsideredChildPughclassA
(wellcompensateddisease)7to9isclassB(significantfunctionalcompromise)and10to15isclassC(decompensateddisease).Theseclasses
correlatewithoneandtwoyearpatientsurvival:classA:100and85percentclassB:80and60percentandclassC:45and35percent.

INR:internationalnormalizedratio.

Graphic78401Version11.0
ChildTurcotteclassificationofpatientswithcirrhosis

Parameter A B C

Ascites None Easilycontrolled Poorlycontrolled

Bilirubin <2mg/dL(<34.2micromol/liter) 2to3mg/dL(34.2to51.3micromol/liter) >3mg/dL(>51.3micromol/liter)

Albumin >3.5g/dL(>35g/liter) 3.0to3.5g/dL(30to35g/liter) <3.0g/dL(<30g/liter)

Encephalopathy None Mild Advanced

Nutritionalstatus Excellent Good Poor

Graphic56436Version3.0
ContributorDisclosures
EricGoldberg,MD Nothingtodisclose SanjivChopra,MD,MACP Nothingtodisclose BruceARunyon,MD Nothingto
disclose KristenMRobson,MD,MBA,FACG Consultant/AdvisoryBoards:ActavisPharmaInc.[IBSD(Eluxadoline)].

Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.

Conflictofinterestpolicy