外文翻译-- Prognostic Model for the Patients with Severe.PDF

PrognosticModelforthePatientswithSevereLiverDiseaseWenfangWu1*,JingZhang,BinrongMa,JinqiuHe,LunliZhang,ChunyiZou,ShaojieXin,ChangyanLin*1*DepartmentofBiologyMedicalEngineeringCapitalMedicalUniversity,100069Beijing,C*BeijingAnZhenHospitalBeijing,ChinaAbstracttoanalyzeprognosticfactorsofpatientswithsevereliverdiseaseanddevelopaprognosticmodelforthemwhichisfitfultothecharacteristicsofourcountry.FromMarch2002toJune2007,the527patientswithsevereliverdiseasewereevaluated,thefollow-upinformationwerecollectedincludethesurvivalstate(death/survival).ThesurvivalmodelwasestablishedbyusingCOXproportionalhazardmodel.New400caseswereusedtotestandevaluatethedecisioncapabilityofthemodel.NineprognosticfactorswereextractedbyusingCOX,theprognosticindex(PI)wascalculated.BystatisticsanalyzetocomparetheROCarea(AUC)ofthissystemmodelwithCTPandMELD,thissystemmeldisbetterthanCTPandMELD.Thedevelopedmodelisfitfultothecharacteristicsofourcountrywheretherearealotofvirushepatitispatients,sothemodelisvaluableinprognosticevaluationofsevereliverpatientsandveryusefultoguidecliniciansinselectingtreatmentmethodsinChina.KeywordsSevereLiverDisease；Prognosis；CoxsproportionalhazardmodelI.IntroductionHepatitisisamajordiseaseinChina.Thedeathrateisabout70%forseverehepatitis.Theresultsfromtheinternalmedicaltherapyarehardtobesatisfactory.Withrapiddevelopmentofscienceandtechnologyinrecentlyyears,artificialliverhasbeenbecominganimportantcuremethodandhasbeenusedbythehospitalsatdifferentlevels.Thematurationoflivertransplantationtechniquemakesitoneofthemosteffectivetherapiesforthepeopleatthefinalstagesoftheliverdisease.However,becauseofthelimitationofliversourceandthehighexpenseforthetreatment,mostofthesuffererscannotbenefitfromit.Therefore,itisthecommonconcernforthesufferersandpersonsworkingontheliverdiseasetochoosepropertreatmentmethodwiththewelltime,soastoimprovethesurvivalrateandtheirlifequality.Thekeytosolvethisproblemistheprognosiswithhighprecisionandproperevaluationofthediseaseanditstherapy.Foryears,multipleresearcheshavebeenconductedforprognosisjudgmentoftheliverdisease.ThemostsignificantaretheChild-Turcotte-Pugh（CTP）classificationandmodelforend-stageliverdisease(MELD),whichhavebeenwidelyusedtoprognosisofthefinalstageofliverdisease,esp,thehepatocirrhosis,andhavebeenthebasisoftheliverdistributionforitstransplantation.However,virusisthemainreasonfortheliverdiseaseinourcountry.Thehighoccurringrateofhepatocirrhosisfromthehepatitisandchronicseverehepatitisisdifferentfromitsacutebreak-outinabroad.Therefore,theprognosissystemfromothercountriesisnotalwaysapplicabletoourcountry.Theresearchersinourcountryaretryingtofindouttheprognosisguidelinethatissuitabletothesituationofourcountry,toconstructtheprognosissystemforthesufferersofliverdiseases,esp,forthevirushepatitis.However,therehavebeennoreportofthestudywithbigsample,multiplecenters,andwithlongtimesurvivinganalysisbasedonthefollow-upsurvey.DataandMethodsA.CasechoicesAccordingtopreventionandcureprojectofthehepatitis(2000),527cases,agedfrom14-75,arediagnosedashepatitisandhepatocirrhosisfromMarch2002toJune2007.ThesecasescamefromfivehospitalsincludingtheBeijingYouanHospitalAffiliatedtoCapitalUniversityofMedicalSciences,theNinthPeoplesHospitalofNanchanginJiangXiProvince,theFirstHospitalAffiliatedtotheJiangXiMedicineUniversity,theSixthPeoplesHospitalofDaLianinLiaoNingProvinceandtheProjectNameWuJiePingMedicalFoundation(320.6750.09071)，theCapitalFundofMedicalResearchandDevelopment（20022039）978-1-4244-4713-8/10/$25.002010IEEE302HospitaloftheChinesePeopleArmy.B.Recordingindices(241intotal)znormalindices:Sex,age,diagnosticclassification,diagnosticstages,pathogeny,complications,returnafterleavinghospital,inducementofdisease,etc.zcomplications:theinformationofasciticfluid，HCD,HRS,alimentarytracthemorrhage,pleuraleffusion,spontaneousperitonitis,disturbanceofacid-basebalanceandothercomplications.zLaboratoryandmedicalimagingindicesliverfunctionalandbiochemicalindices,bloodroutineexaminationindices,bloodcoagulatingindices,pathogenindices；andimagingindices.C.AnalysismethodsandstatisticalmethodsSurvivingstatus(aliveordead)ofthesuffererwasrecorded.Thecurrentbodystatus(livertransplantation,hepatocirrhosis,chronichepatitis,andhealthetc)wererecordedforthealive,whilethetime(daysinprecision)andthereason(liverdiseaseornot,toexcludethedeathfromotherdisease)forthedeathwererecorded.AdatabasewasconstructedwithEpidata3.02basedonallthesematerials,includingalltheindicesrecordedandresultsfromthefollow-upvisiting.TheCoxproportional-hazardsregressionanalysis(builtinSPSS13.0)wasappliedtothedata.Theregressionequationswerecreatedfromthegroupoftheindiceswhichcanreflecttheprognosisoftheseverehepatitis.Statisticalsignificancewasdefinedasp=0.05.ResultsA.Resultsofstatisticalanalysis1)Themainindicesoftheroutineexaminationa)DistributionofetiologicalagentsintheselectedsufferersIntheselected527cases,6(1.1%)arehepatitisI；406(77.0%)arehepatitisII；2(0.4%)arehepatitisIII；26(4.9%)arehepatitisV；56(10.6%)aremixed；4(0.8%)aredrugrelated；4(0.8%)arealcoholrelated；1(0.2%)isself-immunerelated；and22(4.2%)arefromothersource.b)DiagnosisoftheselectedcasesInthe527selectedcases,39(7.4%)casesareacuteseverehepatitis,51(9.7%)aresubacuteseverehepatitis,chronicseverehepatitisare405(76.9%),andchronichepatitis（trendingtosevere）are32(6.0%).c)AlimentarytracthemorrhagewhendiagnosedWhendiagnosed,nobleedinginthealimentarycanalwasfoundin433cases(82.2%),whiletheother94cases(17.8%)werefoundbleeding.d)AsciteswhendiagnosedIntheselected527cases,255(48.4%)havenoascites,124(23.5%)caseshavesmallamountofascites,83(15.7%)middleamount,and65(12.3%)caseshavelargeamount.2)StatisticalresultsofauxiliaryexanimationOfthe527selectedcases,themainindicesfromthelaboratoryandmedicalimagingexaminationareshowninTable1.TABLE1VariableInformationofAuxiliaryExanimationvariablmmmsALT(u/l2951AST(u/l2951AST/A-1-0TBIL(m0520DBIL(-420d/t-0ALB(g/2330CHO(m1640CR(mg/-1-0PT(s)2530INR0210PTA-0-0Note:allvaluesisnaturallogarithminthetable3)SurvivalofthesufferersTable2showsthesurvivalinformationofthe527patients.B.ScreeningoftheindependentprognosticfactorsFifty-twoindices,criticaltothesurvivaltimeofthepatients,wasselectedfromtheoriginal241indices,whicharefromthesurvivalanalysisofKaplan-Meiermethods,andstatisticalanalysis(theLog-RanktestandBreslowtest)tothesurvivalrateofpatientsinthenearandfarfuture.Classificationmethodswereappliedtothe52indicestoreducetheeffectsofthepossiblemultivariableco-dependence.Theresulting33indicesfromtheclassificationmethodcouldbeusedtoconstructtheregressionmodel.TABLE2SurvivalInformationofPatientsgroupNpercentsurvivaltime30daysofsurvivaltime60daysofsurvivaltime90daysofsurvivaltime180daysofsurvivaltimeoneyearofsurvivaltimedeath35867.951.1(18.5)12.8(11.0)18.8(16.0)21.1(17.0)35.7(17.0)28.7(18.0)survival16932.1682.7(611.0)30.060.090.0180.0360.0total527100.0253.7(34)21.9(30)35.5(34.0)47.2(34.0)79.6(34.0)141.3(34.0)Note:everyvaluebetweenparenthesesismedianinthetableC.ConstructionoftheregressionequationCoxproportional-hazardregressionwasappliedtothe33indicesfromtheaboveanalysis.ThePvaluewassettobelessthan0.05forthevariablesacceptedorremovedfromthemodel.X2testwasappliedtotheregressionequationfittingprocess,inwhichtheX2valueis145.3(p0.001).Nineindiceswerefinallyretainedintheregressionequation.Whichwerealimentarytracthemorrhage(h43),age,degreeofascites(c5),ALTinitsnaturallogarithm,AST/ALTinnaturallogarithm,TBILinnaturallogarithm；（mg/dl）,CHinnaturallogarithm,Cr(mg/dl)innaturallogarithm,andPTAinnaturallogarithm.Table3showsalltheindicesretainedintheregressionequation.ThebaselinecumhazardofregressionmodelislistedinTable4.Inthisstudy,theprognosticindexformulationfortheseverehepatitissufferersis:PI=0.493h43+0.028age+0.189c5+0.233lnalt+0.379ln(ast/alt)+0.424lntbil-0.369lnch+0.17lncr-0.899lnptaThecumulativesurvivalfunctionoftheeachsuffererinstagescanbecalculatewiththisformula:)(0)(,)()(thpietsethth=wherepiisprognosticindex,h0(t)isbaselinecumhazard,h(t)iscumhazard，s(t)iscumsurvival.TABLE3VariableInformationinCoxFunctionVariableBSEWaldPORH43.493.14910.990.0011.637AGE.028.00534.832.0001.029C5.189.0629.242.0021.208LNALT.233.07011.003.0011.262LNASTALT.379.1269.040.0031.461LNTBIL.424.1389.470.0021.528LNCH-.369.11310.715.001.691LNCR.170.0853.988.0461.186LNPTA-.899.14041.102.000.407TABLE4BaselineCumHazardofModeltime30d60d90d180d360dh0(t)baselinecumhazard0.0170.0250.0270.0290.030D.ComparisonbetweenresultsfromtheprognosticmodelinthisstudyandthosefromCTPandMELDInordertoverifytheresultsofthisstudy,theinformationof400patientswascollected.Foreachpatient,thecumsurvival,CTPscore,andMELDscorearecalculated.TheRoccurveandtheareaunderthecurveareusedtoestimatetheveracityofthepatientssurvivalindifferentstagessuchas30days,60days,90days,180daysandoneyear.Asthestatisticalresultsfromtable5and6,theregressionmodelinthisstudyhasbetterpredictionatthedifferentstagesthantheCTPandMELDmodel.Therefore,themodelinthisstudyismoreapplicabletoliverdiseasesufferersinourcountry.TABLE5AUCofThreeModelsmodeltime30d60d90d180d360dctp61.962.562.062.862.2meld68.464.663.362.062.2thissystemmodel78.280.179.278.978.5TABLE6AUCsComparisonofThreeModelstimecomparewithctpcomparewithmeldzpzp30d4.090.012.510.0560d4.400.013.950.0190d4.240.013.990.01180d3.900.014.100.01360d3.950.013.950.01.DiscussionsInthisstudy,aprognosticformula,suitabletothesituationofChinaandtoestimatetheprognosisofseverehepatitisandliverfunctionfailure,wasderivedbasedonCoxproportional-hazardregressionmodelanalysisofthedatafromtheinpatientsandtheirfollow-upsurvey.Thesedatawerecollectedfromalargepoolofsamplesfromdifferenthospitalsaroundthecounty.Theriskprognosticformuladerivedfromthisstudyinclude9indiceswhichareregularlyusedinclinical:alimentarytracthemorrhage,age,degreeofascites,ALTinnaturallogarithm,AST/ALTinnaturallogarithm,TBIL（mg/dl）innaturallogarithm；CHinnaturallogarithm,Cr(mg/dl)innaturallogarithm,andPTAinnaturallogarithm.TheTBILanddegreeofascitesaresameasthoseinCTPscoringandclassification.TherearecorrelationsbetweenthePTAandthePTintheCTPscoringsystem.CRandTBILaresameasthoseintheMELDmodelwhicharebeingwidelyusedinabroad.Alimentarytracthemorrhageandascitesarecomplicationsusuallyseenintheseverehepatitispatientandoneofthemajorreasonsleadingtothedeathofpatients.Anyexpertofliverdiseaseagreesthatthesetwocomplicationsarethefirsthandthreattopatientslife,sincethesepatientshavebadprognosis.Previousfindingsindicatethatprognosisbecomeworsewithage.Itwasreportedthatprognosisisbadwhenageisover50andthatthedeathrateweretheleastbetweenagesof31-40.TheincreaseofALTreflectsdegreeoftheinflammation.Itchangeswiththedevelopmentofdisease.IftheincreaseofALTiscompaniedbytheseverityoficterus,prognosisisbad.Inrecentyears,AST/ALThasbeenwidelyusedtoaccesstheliverdiseasedevelopment.Someresearchesshowthattheratioofthemishighlyrelatedwiththedegreeoftheliverfibrosiscausedbythechronichepatitisformanyreasons,andrelatedwithdegreeofthehepatocirrhosis-increaseoftheratioindicatesmoredamageoftheliverfunction.TheconclusionofsomereviewpaperswasthatAST/ALTisareliableindexinestimatingwhetherthechronicsuffererscausedbythehepatitisCvirusarethestageoffibrosisorstageofhepatocirrhosis.HeumannsstudysuggestedthatthecontinuousincreaseoftheAST/ALTindicatedincreaseofthedeathriskforthesuffererscausedbyhepatitisCvirus.Recently,GianninisstudyshowedthatthecombinationofAST/ALTwiththeMELDmodelcanimprovetheveracityofthemedium-termandshort-termprognosisofsufferers.TheratioofAST/ALTappeasesintheequationsofthethisstudypromptthatthisprognosismodelismoresuitedtobeusedinChina,especiallybecauseofthefactthatthereasonsoftheliverdiseasesaremainlyvirus-related.TheincreaseofTBILrepresentsthewidedamageoftheli