DOI10.

3233/DMA-2011-0836 IOSPress

DiseaseMarkers31(2011)139146

Prognosticmarkersinpatientswitha scites andhepatorenalsyndrome

LeylaNazala andAndresCardenasb,
Gastroenterology Department, Air Force Hospital, Santiago,Chile GI/EndoscopyUnit, Institut de Malalties Digestives i Metaboliques,Hospital Clnic, University of Barcelona, Barcelona,Spain

1.

Introduction

mic hyponatremiaandHRS.

Cirrhosisisaprogressiveliverdisordercharacterize d byadistortedliverarchitectureduetobrosiswhich eventuallyleadstoportalhypertension.Itisacomm on causeofmortalityaccountingforover26,000death s annuallyintheUnitedStates[1]. Thenaturalcourse ofpatientswithcirrhosisisfrequentlycomplicated by theaccumulationofuidintheperitonealspaceint he formofascites. Thisiscausedbyanabnormalregulationofextracellularuidvolumewhichleadstoalterationsinrenalfunctionwithrenalsodiumretenti on, solutefreewaterretention,andrenalvasoconstriction. Thesechangesareresponsibleforuidaccumulati on intheformofascites,dilutionalhyponatremiaandh ep- atorenalsyndrome(HRS)respectively. Ascitesisthe mostcommoncomplicationofcirrhosisandposesa nd increasedriskforinfections,renalfailureandmorta l- ity. Patients with cirrhosis and ascites have a poor prognosisanditisestimatedthatnearlyhalfofthese individualswilldieinapproximately5yearswithout livertransplantation.Hypervolemichyponatremi aand HRSoccurlaterandconferanevenaworseprognosi s. Thisarticlereviewscommonprognosticmarkersan d modelsincirrhoticpatientswithascites,hypervole

2 .
A s c i t e s A s c i t e s i s d e n e d a s a p a t h o l o g i

calaccumulationof freeuidintheperitonealcavity. Thedevelopmentof ascitesinapatientwithcirrhosisdenesamileston e asitisaconditionassociatedwithpoorprognosis.Pa tientswithcompensatedcirrhosishavea30%riskof developingascitesat5years. Thosethatdevelopasciteshaveaprobabilityofsurvivalof85%at1year and56%at5yearsiftheydonotreceivelivertransplantation[2]. However,individualsurvivalvariesaccordingtothedegreeofsodiumretention,response to diureticsorassociatedcomplications(i.e.hemorrh age, infectionsorhepatocellularcarcinoma). Itisconsid-

eredthatpatientswitharstonsetofasciteshavebe t- ter survivalthan thosewith previousepisodesof as- cites[3]. Additionally,patientswithmildtomoderate ascites(whohavegoodresponsetotreatment)hav ea betterprognosisthanpatientswithrefractoryascit es. The developmentof refractory ascites, characterized byaninabilitytoresolveasciteswithstandardmedicaltreatment,isassociatedwithshorttermmortalit y andisamarkerofpoorprognosiswith survivalrate of about50% at oneyear [4]. A numberof factors associatedwithpoorprognosishavebeenidentie din patientswithcirrhosisandascites(Table1). Themost importantfactorsinthepredictionofpoorprognosi s ? Correspondingauthor:AndresCardenas,MD,MMSc,GIUnit/arehighChildPughscores,increasedserumcreatinine, InstitutdeMalaltiesDigestivesiMetaboliques,UniversityofB hyponatremia,intensesodiumretention(u arcerinesodium lona, Hospital Clinic Villarroel 170, Esc32, lessthan10mEq/day),andlowarterialpress 08036Barcelona, ure[5]. Spain. Tel.: +34 93 227 5513; Fax: +34 93 227 9850; EISSN0278-0240/11/$27.50 2011IOSPressandtheauthors. Allrightsreserved

140

L . N a z a l a n d A . C a r d e n a s / P r o g n o s t i c m a r k e r s i n p a t i e n t s w i t h a s c i t e s a n d h

epatore

nal syndrome

ease. Furthermore,ithasbeendescribedthatascites relatedvariablessuchastheasciticuidproteinconwithascites

centrationandpreviousepisodesofspontaneousb acterialperitonitis(SBP)addprognosticinformationt o theChildPughScore[4,6]. Alowtotalproteinconcentrationintheasciticuid( < 15gm/L)isassociated withanincreasedriskofSBPandinselectedpatients mayindicateaneedforantibioticprophylaxiswitho ral quinolonestoreducetheriskofSBPandHRS[6].

3.

Liver function

Exploratory poor Patients with low arterial ndings : pres- sure(meanarterialpressure Absenceo 82mmHg)haveapoor prognosis compared to hepatom patients with normal arterial pressure[5,9]. galy Poornutri Recentstudieshaveshownthat,inad- dition to onalstatu the vascular disturbances, a relative inadePreviousa quacy of cardiac output contributes to the cites renal hy- poperfusion mainly in advanced HRS. Lowarteri lpressure Recent trials haveshownthatpatientswithascitesandacardiaciEsophage alvarices nLivertests dexbelow1.5l/min/m2hadapoorersurvivalat3,9, Highseru

Ta ble 1 prognosis Ad [5].

Anumberofstudieshaveshownthatparametersof liverfunctioncorrelatewithprognosisandmaybeu sefulinclinicalpracticetoestimatesurvivalinthegen eral populationofpatientswithcirrhosis[7,8]. Itisthereforenotsurprisingthatsomeliverfunctiontestshav e astrongprognosticvalueinpatientswithcirrhosisa nd ascites. Anincreasedserumbilirubinlevelorreduced serumalbuminlevelisassociatedwithashortsurvi val inthesepatients[9,10]. Bycontrast,prothrombinactivityhasnopredictivevalueinpatientswithascites [5, 9,10]. Thislackofpredictivevaluemaybeduetothe factthattheprolongationofprothrombintimeinpatientswithcirrhosisoccursverylateintheevolution of thedisease.Inotherdiseasestatessuchasprimary biliarycirrhosisorprimarysclerosingcholangitisbiliru binlevelsinconjunctionwithalbuminareconsidere d verygoodmarkersofprognosis[11].

mbilirubin Lowserum albumin Renaltests Dilutiona hyponatr mia Lowurine odium Increased serumcre tinine Reducedw aterexcre ionafterw terload Circulatory abnormaliti s Lowarteri lbloodpre sure Highplasm areninact vity Highplasm aaldoster ne Highplasm anorepine phrine

4.

Circulatoryfunction

Thedevelopmentofsystemichemodynamicdistur - bancesin cirrhoticpatients leadsto effectivehypovolemia,arterialhypotension,overactivityofvasoc on- strictorsystemsincludingthereninangiotensinsystem andthesympatheticnervoussystemandnonosmotic hypersecretionofargininevasopressin(AVP).This circulatorydysfunctioninpatientswithcirrhosisanda scitesalsocorrelateswithsurvivalandisamarkerof

Measurem ents of renal and hormona functions ouldbeob ainedafte aminimumof4d aysonalo sodiumdi tand withoutdi retics.

a n d 1 2

monthsthanthosewithacardiacindexabove 1.5l/min/m2[12].Theactivityofvasoconstrictorsy s- tems also has prognostic value in cirrhosis with as- cites. Approximately30%ofpatientswith cirrhosis andasciteshavenormallevelsofplasmareninactiv ityandaldosterone. Thesepatientshaveabettersur- vival compared to patients with abnormal values of theseparameters[5,9,13].Patientswithincreased plasmareninactivityandincreasedaldosteroneandnor epinephrinelevelsalsohaveahighprobabilityofdev el- opingHRS[14,15].

5.

Renal function

Renaldysfunctionincirrhosisisaconsequenceof

circulatory disturbance, characterized by a low systemicvascularresistanceanddecreasedeffective arterialvolumewhichleadstorenalvasoconstrictionan d HRS[14,16,17].Theseveritiesofrenalandcirculat ory dysfunctionarewellestablishedprognosticfactors in patientswithcirrhosisandascites. Infactsodiumretention,ahighlyprevalentrenalfunctionabnormali ty ofcirrhosis,isassociatedwithreducedsurvival[13] . Sodiumexcretionshould ideally be measured in pa- tientsonalow-sodiumdietof70 90mEq/dayduring 57daysandoffdiuretics. Thisparametermayindicateprognosisinpatientswithcirrhosisandascites [5, 9]. Thosewhohaveasodiumexcretiongreaterthan

L.NazalandA.C

1 ardenas/Pr 4 ticmarkersin 1 nts

withascitesa patorenal syndrome

Fig.1.Longtermsurvivalaccordingtosodiumexcretioninaseriesofpatientswithcirrhosisadmittedtothehospitalforthetreatmentofascites.

sodiumintakehaveagoodprognosis,butpatientsw ith amarkedlyreducedsodiumexcretion( < 10meq/L)in relationwiththeirintakehaveapooroutcome[5,9,1 3, 18](Fig.1). Animpairedabilitytoexcretesolute-freewatercorrelateswithlong-termprognosisincirrhosiswithascitesbecauseitreectstheintensityofneurohumor al andcirculatorydysfunctionpresentinthesepatien ts[9, 19].Patientswithpreservedrenalabilitytoexcretef ree waterhaveabettersurvivalthanpatientswithmark edly impairedwaterexcretion[9,19]. Thepredictivevalue ofwaterexcretionintheevaluationoflong-termsurvivalwasconrmedinalargeseriesofcirrhoticpatientsadmittedtoasingleinstitutionforthetreatme nt ofascites[9].Survivalestimatesforpatientswithno rmaldiuresis( > 8mL/min)afterawaterload(20mL/kg bodyweightof5%dextroseIV)at1,5and10yearsof follow-upwere85,41and32%. Correspondingvaluesforpatientswithmoderatelyreduced(3 8mL/min) orseverely-reduced( < 3mL/min)diuresisafterwater loadwereonly55,26and13%,and37,13and3%,

respectively.Inthisstudy,waterexcretionwasthep e r arameterwiththestrongestprognosticvaluecompa D red tootherparametersassessed. Renalfailureincirrhosisisdenedasanincreasei i n s serumcreatinine > 1.5mg/dl(20). e a Renalfunctionas assessedwithserumcreatinineisanimportantmars e ker ofprognosisinpatientswithadvancedcirrhosis.Inf ( act thecurrentallocationsystemoflivertransplantatioM E nin theUnitedStatesandothercountriesincludesseru L m creatinineasavariableintheModelforEnd-D ) StageLivs c o r i n g s y s t e m

. Renal function canbeestimatedbyassessingglomerularltration rate (GFR)eitherwiththeserumcreatininelevel,formul as thatestimate GFR, or directclearancemethodswith exogenousmarkers(21 23).Howeverthemostwidely usedparametertoestimateGFRinclinicalpracticei s serumcreatinine(21).Slightincreasesinserumcre atinine(from1.2to1.5mg/dl)areindicativeofreductio ns inGFRandareassociatedwithreducedsurvival.Ho wever,serumcreatinineishighlyinuencedbyfactor s suchasdecreasedmusclemassandproteinintake, so itcanoverestimaterenalfunctioninpatientswithcir rhosis[22,23].Overestimationofrenalfunctionocc urs moreofteninpatientswithaverylowGFR. Theetiologyofrenalinsufciencyinpatientswith cirrhosisalsohasaprognosticvalueinpatientswith

cirrhosis[24]. Themostcommoncausesofrenalfailureinthesepatientsarebacterialinfectionsandvol umedepletioncausedbybleedingoruidlosses.Dr ug inducedrenalfailure(mainlyfromnonsteroidalantiinammatorydrugs(NSAIDs)andintrinsicrenaldis eases(mainlyglomerulardiseaseassociatedwitha lcoholicliverdisease,hepatitisBorCinfectionorother chronickidneydiseases)arelesscommoncauses. In arecentprospectivestudyof562patientsadmitted to tertiaryhospitalfordecompensatedcirrhosisina6 year period[24],themostfrequentcauseofrenaldysfun ctionwasrenalfailureassociatedwithinfections,ma in- lySBP(46%),followedbyhypovolemiarelatedrenal failure(32%),HRS(13%),andparenchymalnephro pa- thy(9%). The3monthprobabilityofsurvivalforall

142

L . N a z a l a n d A . C a r d e n a s / P r o g n o s t i c m a r k e r s i n p a t i e n t s w i t h a s c i t e s a n d h

epatore nal syndro me

Table2 Childpughclassicationandmodelforend-stageliverdiseasemodelMELD ChildPughClassication 1 2 3 Ascites Absent Mild Moderate Encephalopathy Absent 12 Bilirubinmg/dL

34

<

223

>

Bilirubinmg/dL Albumingr/L INR

<4410>10 >3,5 2,83,5<2,8 <1,7 1,82,3>2,3 ChildA:56points;ChildB:710points,ChildC 1015points Score Components MELDScore 9,2 loge(creatininemg/dL) + 3,8loge(bilirubinmg/dL) + 11,2loge(INR)+ 6,4 MELDSodium MELD+1,59 (135NamEq/L) ? Values ofcreatinine, bilirrubin, INR lower than 1are rounded to1. Serum creatininevaluesabove4mg/dLareroundedto4. Patientsonhemodyalisisare givenacreatininevalueof4mg/dL.MELDscoresrangedfrom6to40p oints. Valuesofserumsodiumbelow120mEq/Lareroundedto120. Valuesover 135mEq/Lareroundedto135. INR:internationalnormalizedratio.

causes of renal insufciency was 38% with a mediansurvivalofonly41days. Patientswithparenchymalnephropathyhadthebestsurvival(73%prob abilityofsurvivalat3months),followedbypatientswi th hypovolemia-relatedrenalfailure,whohada3month probabilityofsurvivalof46%.Patientswithrenalf ailureassociatedwithinfectionsandthosewithHRS had thelowest3monthprobabilityofsurvival,whichwas 31and15%,respectively. 6. Hyponatremia Hyponatremiaiscommoninadvancedcirrhosi sand isusuallyrelatedtoimpairedsolutefreewaterexcretionprimarilyduetoincreasedcirculatinglevelso fAVP whichresultsinadisproportionateretentionofwa ter relativetosodium. 135mEq/Lwas49%;withlevel 130mEq/L, 125 s mEq/L,an 120mEq/Lwas21.6%,5.7%,and1.2 d %,

associatedwiththedevelopmentofotherco mplications ofcirrhosis.Patientswithhyponatremiahav emoresevereliverdisease,worsecontroloftheirascit es,ahigherrateofhepaticencephalopathy,SBPandH RSwhen comparedwithpatientswithouthyponatre mia(26,27) Regardless,bothserumsodiumandserumc reatinine areindependentprognosticfactorsofpooro utcomein patientswithcirrhosis. Thisisimportantsincerenal function(serumcreatinine)isavariableincl udedinthe MELDscoringsystemforallocationoforgan sinliver transplantation. HyponatremiaalsohasclinicalimplicationsinpatientsundergoingLT.Patientsth atundergolivertransplantationwithhyponatremia maybeat riskforneurologicalcomplications,renalfail accuratepredictionofsurvivalinaspecicpatient. As mentionedabove,anumberofvariableswithprogn os-

respectively[2]. Inpatientswithrefractoryascitesor HRS, this proportion may increase up to 50% [26]. Sincehypervolemichyponatremiaiscomplicatio

ticvalue,particularlythosethatthattakeint oaccount renalandcirculatoryfunctionhavebeenide ntiedin thesepatients.Nonethelessonlyoneprogn

L.NazalandA.Cardenas/Prognosticmarkersinpatients withascitesandhepatorenal syndrome

143

awaterload,meanarterialpressure,ChildPughclass, andserumcreatinine)hasbeenproposed,however this test hasnotgainedacceptanceand maynotbeeasilyapplicableinallcenters[9]. Forseveraldecades, theChildPughclassicationhasbeenusedinclinical practiceto estimatesurvivalof patientswith ascites. Thisclassicationwasoriginallydesignedtoestima te theriskofdeathincirrhoticpatientssubmittedtosur gicalportosystemicshuntsforthetreatmentofportal hypertension[30,33,34]. Thissystemincludesvariables suchasascites,encephalopathy,serumbilirubin,s erum albumin,andprothrombintime. Subsequenttoitsapplicationtoestimatesurgicalrisk,theuseofChildPugh classication wasvalidatedandextendedtoevaluate longtermprognosisofcirrhosis[35,36].ThesimplicityoftheChildPughclassicationdetermineditswide useasprognosticmodeltoevaluatesurvivalincirrh osis. However,theChildPughclassicationhassome drawbacksthatlimititsuseasprognosticclassicat ion forpatientswithascites.First,itdoesnotincludevari ablesofrenalorcirculatoryfunction,whichareknow n tobeveryimportantprognosticfactorsinthesepati ents. Second,prothrombintimewhichisoneofthevariabl es includedintheclassicationhaslittleprognosticval ue inpatientswithascites[5,10]. Third,thescoredoes notdistinguishpatientswithserumbilirubinvalues of 10mg/dLor20mg/dLorhigher.Lastly,theChildPugh classicationincludeshepaticencephalopathyan dascites,twomeasuresthataresubjecttoawideclinica l interpretationandaremuchlessobjective. Themain problemwiththeChildPughclassicationisforpatientsthatbelongtotheChildPughclassB.Itiswell knownthatChildPughclassApatientsusuallyshow goodmidtermsurvivalwithouttransplantationunl ess othercomplicationsoccur,whileChildPughclassC patientsareconsideredtheconventionalcandidat

esfor livertransplant.However,Child-a PughclassBpatients s areaheterogeneousgroupinwhichpatientscouldr t eh mainstableforalongperiodorontheotherhandcan e suddenlydeteriorateintoclassC.Althoughthesepi M tE fallswereknownforyears,nootherprognosticmod L el D ofwideapplicabilityandobjectivemeasureshadbe M en identied. o TheMELDscorewascreatedinaimsofbetterpre- d dictingsurvivalinpatientsundergoingatransjugul e l ar intrahepaticshunt(TIPS)placement[32].Inthismo t o d- el, INR,totalserumbilirubinlevel,serumcreatinine e level, and etiology of cirrhosis were used to s predict survivalfollowingplacementofaTIPSforanycause.t Thisprognosticindexwasmodiedbyremovingthea etiology and then implemented in the United b l States i s h p r i o r i t y o f p a t i e n t s a w a i t i n g l i v

ertransplantation[32]. Theadvantagesof thissystemarethatvariablesareobjectiveandpred ictive.Forinstance,bilirubinisarobustvariablealsoin cludedintheChildPughclassication;renaldysfunctionisawellknownvariableassociatedwith apoor prognosisin cirrhoticpatients; and INRis theinternationalnormalizedratioforprothrombintime. The MELDmodelisalsopracticalforintheriskstraticationofpatientsundergoingTIPS,shorttermsurvival predictionofHRSandacutevaricealbleeding[37 39] andrisk stratication for nontransplantsurgery[40, 41].MELDhasadvantagesoverChildPughbecause it includesvariablesrelatedtobothliverandrenalfun ction.Thisscorealsoexcludessubjectivevariables,li ke encephalopathyandascites. Nevertheless,studiesindicatethatsomesubsetsofpatientswithcirrhosism ay have high mortality despite low MELD scores [42]. Althoughpatientswithasciteswithseveresodiumr etentionanddilutionalhyponatremiahaveapoorpro gnosis,theymayhavealowMELDscoreiftheyhave normalcreatininelevels. SincehyponatremiaandimpairedsolutefreewaterexcretionareeventsassociatedtodevelopmentofHRSandhavebeenassociate d withincreasedliverrelatedmortality[43]theaddition

ofserumsodiumtoMELDscore(MELD-Na)hasbeen proposedasbetterprognosticmodelinpatientsaw aitinglivertransplantation[44].InastudyfromtheUS A theabilityofserumsodiumtoaddprognosticcapabi litytotheMELDscorewasanalyzedinadultprimary livertransplantcandidateswithcirrhosisregistere dfor transplantationduring2005and2006[45]. Boththe MELDscoreandtheserumsodiumconcentrationw ere predictorsofmortalityandwhencombinedintoane w MELDNascore,thosepatientswithlowMELDscores benetedmostfromthenewscoringsystem.Altho ugh themost acceptedprognosticmodelin patientswith cirrhosisawaitingLTinUSAandseveralothercountriesistheMELDscore,theChild-Pughclassstillis consideredanimportantprognosticfactorspecic ally inthosethatarebeingconsideredforsurgeryorano ther majorintervention.

8.

Hepatorenalsyndrome

HRSisapre-renalrenalfailurewithoutanyidentiablekidneypathologythatoccursinpatientswitha dvancedcirrhosis[20].Duetothelackofspecicdiag nosticmarkers,thediagnosisofHRSiscurrentlyma de usingcriteriatoexcludeothercausesofrenalfailure

144

L.Na zala ndA. C arde nas/ Prog nosti cmar kersi npati ents with ascit esan dhep atore nal synd rome Table3 D i a g n o s t i c c r i t e r i a o f h e p a t o r e n a l s

y n d r o m e i n c i r r h o s i s 1 . C i r r h o s i s w i t h a s c i t e s 2.Ser umcr eatin ine > 1.5m g/dL 3.Noi mpro vem entof seru

mcreatinine(decreasetoalevellowerthan1.5mg/dLafteratleasttwodaysoff diureticsandvolumeexpansionwithalbumin(1g/kgbodyweightuptoamaximumof100g/day) 4.Absenceofshock 5.Nocurrentorrecenttreatmentwithnephrotoxicdrugs 6.Absenceofsignsofparenchymalrenaldisease,assuggestedbyproteinuria( > 500mg/day)orhematuria ( <50redbloodcellsperhighpowereld),and/orabnormalrenalultrasound. ? Salernoetal.Diagnosis,preventionandtreatmentofthehepatorenalsyndromeincirrhosis. Aconsensus workshopoftheinternationalascitesclub, Gut 56 (2007),13101318.

Fig.2.Survivalofpatientswithcirrhosisafterthediagnosisoftype1andtype2hepatorenalsyndrome.

thatcanoccurincirrhosis(Table3). PatientswhodevelopHRShavemoreadvancedliverdiseaseandf eaturesofcirculatorydysfunction,withmarkedhyp otension,lowsystemicvascularresistance,veryhighl evels ofreninactivity,norepinephrineandAVP.Thesep atientsusuallyhavelowurinevolumeandintenses odiumretention,withurinesodium 20mEq/L.TheannualincidenceofHRSinpatientswithascitesisapproximately8%andoccursinabout10%ofhospit alizedpatientswithcirrhosisandascites.Theproba bility ofdevelopingHRSinpatientswithcirrhosisandas cites is18%atoneyearan39%atveyears[14].Therea re twotypesofHRS;inType1HRSrenalfunctiondeterioratesrapidlywithanincreaseinserumcreatini neto

Predictivefactorsassociatedwithagreat erriskofdevelopingHRShavebeendescribedincirrhoti cpatients withasciteswithoutrenalfailure[14,15].Pat ientswith intensesodiumretention(<10mEq/day),s pontaneous dilutionalhyponatremia(serumsodium<1 30mEq/L), alowmeanarterialbloodpressure(<85mm Hg),decreasedcardiacoutput(<6.0L/min),increa sedplasmareninactivity,andincreasedaldosteron eandnorepinephrinelevelshaveahighprobabilityofd eveloping HRS[14].Recentlyithasbeenshownthatcar diacdysfunctionwithreductionofcardiacindex(CI) precedes theHRS[12,15]. Infact, CI isanindependentpredictorofdevelopmentofHRS[15]. Inarecentstudy,

L.NazalandA.Cardenas/Prognosticmarkersinpatients withascitesandhepatorenal syndrome 145 [ ascites, LiverInt 24 (2004),457464. [5] J.Llach,P.Gines,V.Arroyoetal.,Prognosticvalueofarterial 9 pressure,endogenousvasoactivesystems,andrenalfunction ] incirrhoticpatientsadmittedtothehospitalforthetreatment G ofascites, Gastroenterology 94 (1988),482 . 487. F [6] P.Gin`esandA.C e ardenas,Themanagementofascitesanddir lutionalhyponatremiaincirrhosis, SeminLiverDis n a 28 (2008), n 4358. d [7] P.Gin`es,E.Quintero,V.Arroyoetal.,Compensatedcirrhosis: e z naturalhistoryandprognosticfactors, Hepatology 7 (1987), E 122128. [8] P.Schlichting,E.Christensen,P.K.Andersen,L.Fauerholdt, s 9. Summary E. Juhl, H. Poulsen and N. Tygstrup, Prognostic factorsp in a r cirrhosisidentiedbycoxsregressionmodel, Patientswithcirrhosisthatdevelopascites,hypona r Hepatology 3 a (1983),889895. tremiaandHRShaveapoorprognosis.Theprognost c ic h , factorsofthesecomplicationsaremainlyrelatedto A the . underlyingcirculatorydysfunctionthatoccursionp S a- tienstwithcirrhosisatanadvancedstage. a Otherprogn c nosticfactorssuchasliverdysfunctionarealsoimp h ore tantbutdonotseemtohaveamajorinuenceonthe z outcomeofthesepatients. ThemostcommonprogF u nosticmodelsincirrhosisaretheChilde Pughscoreand y theMELDscore,bothincludevariablesthattakeint o o accountliverandrenalfunction. , HowevertheMELD score is the most commonly P . used prognostic model G fororganallocationinlivertransplantcenters. i More n studiesareneededinordertodeneifothervariable e s s e ofcirculatoryandrenaldysfunctionmayimproveth t e prognosticcapabilityofthesemodels. a l . References , A [1] A.M.Minino,M.P.HeronandB.L.Smith,Deaths: Prelimip narydatafor2004, NatlVitalStatRep 54 r (2006),149. o [2] R.Planas,S.Montoliu, B.Ballesteetal.,Naturalhistoryof g patientshospitalizedformanagementofcirrhoticascites, n Clin o s GastroenterolHepatol 4 (2006),13851394. [3] P.Gin`es,A.Cardenas,V.ArroyoandJ.Rod t es,Management i c ofcirrhosisandascites, NEnglJMed 350 m (2004),16461654. [4] R.Moreau,P.Del`egue,F.Pessioneetal.,Clinicalcharactero istics and outcome of patients with cirrhosis and d refractory

typesofHRS[39].ThescorecanbeusefulinthemanagementofpatientswithHRS,particularlyforpatie nts whoarecandidatesforlivertransplantation. Mostpa- tientswithtype1HRShaveaMELDscore 20[39]. AMELDscore > 20inpatientswithHRStype2isassociatedwithpooroutcomecomparedtothatofpati ents withMELD < 20sothesepatientsshouldperhapsbe givenprioritylivertransplantation.

elforpredicting survivalincirrhosis with ascites, JHepatol 34 (2001),4652. [10] F.Salerno,G.Borroni,P.Moseretal.,Survivalandprognosticfactors ofcirrhotic patients withascites: Astudyof134 outpatients, AmJGastroenterol 88 (1993),514 519. [11] A.ParesandJ.Rodes,Naturalhistoryofprimarybiliarycirrhosis, ClinLiverDis 7 (2003),779 794. [12] A. Krag, F. Bendtsen, J.H. Henriksen and S. Moller, Low cardiacoutputpredictsdevelopmentofhepatorenalsyndrome and survival in patients with cirrhosis and ascites, Gut 59 (2010),105110. [13] V.Arroyo,J.Bosch,M.Mauri,F.Ribera,F.Navarro-Lopez andJ.Rodes, Effectofangiotensin-ii blockade onsystemic and hepatic haemodynamics and on the reninangiotensinaldosteronesystemincirrhosiswithascites, EurJClinInvest 11 (1981),221229. [14] A.Gines,A.Escorsell,P.Ginesetal.,Incidence, predictive factors,andprognosisofthehepatorenalsyndromeincirrhosis withascites, Gastroenterology 105 (1993),229 236. [15] L.Ruiz-del-Arbol,A.Monescillo,C.Arocenaetal.,Circulatoryfunctionandhepatorenalsyndromeincirrhosis, Hepatology 42 (2005),439447. [16] S.A.GonzalezandJ.F.Trotter,Renalfunctionandmeld: Beingdirectisbetter, JHepatol 52,622623. [17] P.GinesandM.Guevara,Hyponatremiaincirrhosis: Pathogenesis, clinical signicance, andmanagement, Hepatology 48 (2008),10021010. [18] V.Arroyo,J.Bosch,J.Gaya-Beltranetal.,Plasmareninactivityandurinarysodiumexcretionasprognosticindicatorsin nonazotemiccirrhosiswithascites, AnnInternMed 94 (1981),

198201. ascit [19] P.GinesandM.Guevara,Hyponatremiaincirrhosis: Patho- es: genesis, clinical signicance, andmanagement, Rele Hepatology vanc 2008;48:1002-1010. eofs [20] F.Salerno,A.Gerbes,F.Wongetal.,Diagnosis,preventionerum and treatment of the hepatorenal syndrome in cirrhosis. A sodi consensusworkshopoftheinternationalascitesclub, umc Gut 56 once (2007),13101318. ntrat [21] European Association for the Study of the Liver, P. ion, Gin`es Liver etal.,EASLclinicalpracticeguidelinesonthemanagement ofascites,spontaneousbacterialperitonitis, andhepatorenal Int 30 syndromeincirrhosis, JHepatol 53 (2010),397 (201 417. 0),11 [22] P.Gin`es, A.Cardenas andR.W.Schrier, LiverDisease 37 and theKidney,in: DiseasesoftheKidneyandUrinaryTract 1142 . (8th ed.),R.W.Schriered.,2007,pp.21792205. [23] C.Francoz,D.Glotz,R.MoreauandF.Durand,Theevaluationofrenalfunctionanddiseaseinpatientswithcirrhosis, J Hepatol 52 (2010),605613. [24] M.Martin-Llahi,M.Guevara,A.Torreetal.,Prognosticimportanceofthecauseofrenalfailureinpatientswithcirrhosis, Gastroenterology ,2010Inpress. [25] P.Angeli,F.Wong,H.WatsonandP.Gines,Hyponatremiain cirrhosis: Resultsofapatientpopulationsurvey, Hepatology 44 (2006),15351542. [26] P.Gines,J.Uriz,B.Calahorraetal.,Transjugularintrahepatic portosystemicshuntingversusparacentesis plusalbuminfor refractoryascites incirrhosis, Gastroenterology 123 (2002), 18391847. [27] M.Guevara,M.E.Baccaro,J.Riosetal.,Riskfactorsforhepaticencephalopathy inpatients withcirrhosisandrefractory

146

L.NazalandA.Cardenas/Prognosticmarkersinpatients withascitesandhepatorenal syndrome

Copyright of Disease Markers is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.