肝纤维化的分期：是否到该抛弃肝脏活检的时候作者：肝病专家文章来源：不详点击数：更新时间：2008-12-8StagingLiverFibrosis:TimetoAbandonLiverBiopsy?NezamH.Afdhal,MDChiefofHepatologyBethIsraelDeaconessMedicalCenterAssociateProfessorofMedicineHarvardMedicalSchool传统认为经皮肝活检是评价肝病的公认得金标准。肝活检被用来对肝病作出诊断，对预后进行推断、和进行肝病的分期。尽管对于肝病的血清学诊断试验的进步，肝活检仍然被用来对证实肝病的类型。活检也被用来决定肝病的预后，通常是通过肝
硬化的存在与否来作出判断的。进来，肝活检被用于
病毒性肝炎肝纤维化的分期，进而来为是否需要治疗提供决策依据。更多的专家推荐对于合并间隔纤维化或更严重的患者（METAVIR分期大于等于2期）给予治疗。随着治疗耐受性或有效性的不断提高改变了这一治疗决策，增加了医师和患者接收治疗比率和降低肝活检需要。超声波引导或标记的肝活检轿发生一些严重的并发症是罕见的，出血的几率罕见（1：10000肝活检）。肝活检的主要问题是费用（大约为2200美金）和病人的接收性和
焦虑。此外进来的研究还发现肝活检仅能对80％的患者作出正确的肝纤维化分期，其可能会遗漏30％患者的一些严重的肝纤维化或肝硬化
结节。肝活检所伴有的不准确性与肝病本身的多态性，穿刺标本较小和病理学家的经验有关。这就导致这样一个感念的形成既肝活检至少需要获得25mm长的组织标本以降低标本误差。尽管这是一个病理学目标，但具有临床的难以实现性，仅有约20％的肝活检标本能够达到这一长度。肝活检的局限性导致临床研究者不断地寻找替代方法来为肝病进行分期。非浸入性的血清学生化标记物是最广泛的用来代替肝活检的指标，进来被进行了详细的回顾。有两个重要的生化学试验，他们分别是采用临床变量进行肝纤维化的分期，一些细胞外基质标记物来进行分期。有一些特异性的试验，但从总体上讲这些试验的特点均是相对相似的。试验的准确性通常是通过曲线下面值来界定的。一个理想的试验应该具有100％的敏感性和特异性，那其曲线下面积为1.0。多数已提出的生化试验DD特别是那些临床上较易获得试验，其曲线下面值多在0.80-0.85之间，不能用于疾病分期，但可以将分期为F0/F1的患者从那些纤维化分期为F2-F4的患者中区分出来。因为血清学标记物具有根肝活检相似的准确性，肝活检的准确性约为80％；因此从统计学上讲，生化标记物可能对于肝纤维化的分期效果更佳。有趣的是生化学指标对于疾病的极端情况效果更优，不确定的结果可能发生于分期为F1/F2的患者身上，这并不令人吃惊，因为这些疾病的分期本来就是人为根据疾病进展来进行划分的。肝病分期的一个替代方法是通过纤维化扫描（FibroScan）测定肝脏的坚硬性和弹性。其原理是相对简单的，即通过50mHZ的切变速度传送来对2－5cm的肝脏片断进行测量，然后将其转化为坚硬度的值（单位为千帕，kPA）这一诊断试验的准确性在总体上与那些生化标记物试验是相似的，但其对肝硬化的诊断可能作用更大，曲线下面值达到了0.95。这一试验具有简单，结果的可读性，但这设备仍然处于美国的研究阶段，且是相对昂贵的。联合FibroScan和生化学标记物将增加二者的准确性。现阶段我们能作出什么推荐呢？当诊断是可疑的时候，肝活检仍然是金标准（一定要进行充分的肝活检）。然而，当问题是关于纤维化的分期或治疗决定和排除肝硬化时，生化学标记物和非浸入性检测是合理的首先措施。如果生化指标提示处于疾病的早期或者晚期阶段，就不需进行进一步的评估。当结果是含糊的时候，则需要进行肝活检。最后，我们可以预期之后患者根据每年的生化学和坚硬度扫描就可以预测疾病的进展或好转。在目前这个简单还不是抛弃肝活检用于疾病分期的时候，因为生命之舟随时会结束，而鲨鱼仍环伺在我们周围。Theestablishedgoldstandardfortheevaluationofliverdiseasehastraditionallybeenapercutaneousliverbiopsy.Liverbiopsyisusedpredominantlyforthediagnosis,prognosis,andstagingofliverdisease.Despiteimprovementsinserologicdiagnostictestsforliverdisease,abiopsyisoftenstillindicatedtomakethediagnosisofmanyformsofliverdisease.Biopsyisalsousefulfordeterminingprognosis,usuallybyconfirmingthepresenceorabsenceofcirrhosis.Morerecently,biopsyhasbeenusedforstagingfibrosisinviralhepatitisandfordecisionanalysisastotheneedfortreatment.Manytreatmentalgorithmsrecommendtreatmentforpatientswithseptalfibrosisorgreater（≥METAVIRstage2）.Improvementineithertolerabilityorefficacyoftherapycouldeasilyalterthiscurrenttreatmentparadigm,increasingphysicianandpatientacceptabilityoftherapyandreducingtheneedforliverbiopsy.Liverbiopsyisrarelyassociatedwithseverecomplicationsinthiseraofultrasoundguidanceormarking,andbleedingisrare（1:10,000biopsies）.[1]Themajorissueswithbiopsyarecost（approximately$2200）andpatientacceptabilityandanxiety.Inaddition,recentstudieshavesuggestedthatbiopsyisonlyabout80%accurateinthestagingofliverfibrosisandmayevenmissadvancedfibrosisorcirrhosisin30%ofpatients.Thefactorsassociatedwiththeinaccuracyofbiopsyincludetheheterogeneousnatureofliverdisease,therelativelysmallsizeofabiopsycomparedtothesizeoftheliver,andtheexperienceofthepathologist.Thishasledtotheconceptthataliverbiopsyshouldbeatleast25mminlengthtoreducethesamplingerror.[2]Althoughthisisanobleaimpathologically,itremainsaclinicalrarity,withonly20%ofliverbiopsiesevenapproachingthislength.Theselimitationsofbiopsyhaveledclinicalinvestigatorstostudyalternativemethodstostageliverdisease.Noninvasiveserumbiomarkersarethemostwidelyusedalternativetoliverbiopsyandhaverecentlybeenreviewed.[3]Thereare2majortypesofbiomarkertests,thosethatuseclinicalvariablestostagefibrosisandthosethatuseextracellularmatrix（ECM）markers.[4,5]Thereareadvocatesofspecifictests,butoveralltheperformancecharacteristicsofallthesetestsarerelativelysimilar.Theaccuracyofatestisoftengivenastheareaunderthecurve（AUC）ofthereceiveroperatorcharacteristic（ROC）.Aperfecttestwitha100%sensitivityandspecificitywouldhaveanAUCof1.0.Themajorityofproposedbiomarkertests―andinparticular,thoseavailableforuseinclinicalpractice―haveanAUCofbetween0.80-0.85,notforstagingdisease,butfordifferentiatingmildfrom（F0/F1）fromsignificantfibrosis（F2-F4）.Sincethebiomarkerisvalidatedagainstthebiopsy,andtheaccuracyofthebiopsyisonly80%,itisprobablystatisticallyimpossibleforabiomarkertoperformanybetterforstagingfibrosis.Interestingly,theperformanceofbiomarkersissuperiorattheextremesofdisease;theindeterminateresultsoccurwhenpatientshaveF1/2disease.Thisisnotsurprising,sincethesestagesarerelativelyartificialseparationsofaspectrumofadynamicdiseaseprocess.AnalternativemethodforstagingliverdiseaseistomeasureliverstiffnessorelasticityusingaFibroScan.[6]Theprincipleisrelativelysimpleandinvolvesmeasuringtheshearvelocityofa50mHZwavepropagatedthrougha2-5cmsegmentoftheliver,andconvertingthisintoastiffnessvalueinkilopascals（kPA）.Thediagnosticaccuracyofthetestissimilaroveralltothatreportedforbiomarkers,butitisprobablybetterindiagnosingcirrhosis,withanAUCof0.95.Thetestissimpleandtheresultsreadilyavailable,butthemachineisstillinvestigationalintheUnitedStatesandrelativelyexpensive.CombiningaFibroScanmeasurementwithbiomarkersmayincreasetheaccuracyofbothtests.[7]Whatcanwerecommendatthepresenttime?Certainly,whenthediagnosisisindoubt,aliverbiopsyremainsthegoldstandard（justmakesureitisanadequatebiopsy!）However,whentheissueisstagingoffibrosisforeithertreatmentdecisionorexclusionofcirrhosis,biomarkersandnoninvasivetestsrepresentavalidinitialalternative.Ifthebiomarkersareclearlyindicativeofmildoradvanceddisease,nofurtherevaluationisnecessary,andwheretheyareequivocal,abiopsycansubsequentlybeperformed.Eventuallyonecouldevenanticipatefollowingpatientsonanannualbasiswithbiomarkersandstiffnessscanstofollowtheprogressionorregressionofdisease.Itisnotyettimetoabandonliverbiopsyfordiseasestaging,butthelifeboatsareoutandthesharksarecircling.References1.BravoAA,ShethSG,ChopraS.Liverbiopsy.NEnglJMed.2001;344:495-500.2.BedossaP,DargereD,ParadisV.SamplingvariabilityofliverfibrosisinchronichepatitisC.Hepatology.2003;38:1449-1457.3.AfdhalNH,NunesD.Evaluationofliverfibrosis:aconcisereview.AmJGastroenterol.2004;99:1160-1174.4.Imbert-BismutF,RatziuV,PieroniL,CharlotteF,BenhamouY,PoynardT.BiochemicalmarkersofliverfibrosisinpatientswithhepatitisCvirusinfection:aprospectivestudy.Lancet.2001;357:1069-1075.5.PatelK,GordonSC,JacobsonI,HezodeC,OhE,SmithKM,PawlotskyJM,McHutchisonJG.Evaluationofapanelofnon-invasiveserummarkerstodifferentiatemildfrommoderate-to-advancedliverfibrosisinchronichepatitisCpatients.JHepatol.2004;41:935-942.6.SandrinL,FourquetB,HasquenophJM,YonS,FournierC,MalF,ChristidisC,ZiolM,PouletB,KazemiF,BeaugrandM,PalauR.Transientelastography:anewnoninvasivemethodforassessmentofhepaticfibrosis.UltrasoundMedBiol.2003;29:1705-1713.7.CasteraL,VergniolJ,FoucherJ,LeBailB,ChanteloupE,HaaserM,DarrietM,CouzigouP,DeLedinghenV.Prospectivecomparisonoftransientelastography,Fibrotest,APRI,andliverbiopsyfortheassessmentoffibrosisinchronichepatitisC.Gastroenterology.2005;128:343-350.来源：中华肝病学会中日世纪国际医院研究所我院严格按照国家卫生部规范操作，并严格执行国家卫生部统一制定收费标准，明码标价，杜绝乱收费现象，彻底解决老百姓“看病贵，看病难，看真专家更难”的现象！。了解详情请拨打医院电话：0311-86061304。
