简介:Nonalcoholicfattyliverdisease(NAFLD),definedasabnormalaccumulation(>5%)ofhepatictriglyceridewithoutexcessalcoholintake,isthemostcommonformofchronicliverdiseaseinadultsandchildrenintheUnitedStates.NAFLDencompassesaspectrumofhistologicfindingsincludinguncomplicatedsteatosis,steatosiswithinflammationandsteatohepatitis[nonalcoholicsteatohepatitis(NASH)];thelattercanadvancetocirrhosisandhepatocellularcarcinoma.NASHiscurrentlyacceptedasthehepaticmanifestationofthesetofcardiovascularriskfactorscollectivelyknownasmetabolicsyndrome.In1999asystemforhistologicgradingandstagingforNASHwasproposed;thiswasrevisedbytheNASHClinicalResearchNetworkin2005fortheentirespectrumoflesionsinNAFLD,includingthelesionsandpatternsofpediatricNAFLD,andforapplicationinclinicalresearchtrials.Diagnosisremainsdistinctfromgradeandstage.ArecentEuropeanproposalseparatessteatosisfromactivitytoderiveanumericdiagnosisofNASH.Eventhoughtherehavebeenpromisingadvancementsinnon-invasivetesting,thesetestsarenotyetdetailedenoughtoreplacethefullrangeoffindingsprovidedbyliverbiopsyevaluation.Limitationsofbiopsyareacknowledged,butliverbiopsyremainsthe'goldstandard'fordiagnosisanddeterminationofamountsofnecroinflammatoryactivity,andlocationoffibrosis,aswellasremodelingoftheparenchymainNASH.ThisreviewfocusesonthespecifichistologiclesionsofNAFLDandNASH,gradingandstaging,differentialdiagnosestobeconsidered,andthecontinuingroleoftheliverbiopsyinthisimportantliverdisease.
简介:InordertoobserveseveralantibodiestoliverantigensinChinesepatientswithdifferentfiverdiseasesandtodiscussthecharacteristicsoftheautoantibodiesinautoimmuneliverdiseases,from1412patients,detectedbyindirectimmumofluoreseence(IIF)initially,230patientswithabnormalALTwerechosenanddividedinto5groups:①autoimmunediseasesgroup,42cases:18withautoimmtmehepatitis(AIH),21withprimarybiliarycirrhosis(PBC),3withprimarysclerosingcholangitis(PSC).②HAVgroup,23cases;③HBVgroup,70cases;④HCVgroup,35casesand⑤NonA-Egroup,60cases.First,ANA,AMA,SMA,liver-kidneymicrosomalantibody(LKM)andsoonweretestedby1/F.Then,LKM-1,fivercytosofic-1(LC-1),solubleliverantigen/fiverpancreas(SLA/LP)andsubtypeofAMA(M2)aswellasANAprofilesuchasSS-A,SS-BanddsDNAweretestedbyWesternblotandimmtmoblotstripsassay,respectively.Theresultswerethatamong1412cases,thosediagnosedasAIH,PBCandPSCaccotmtedfor12.7‰,14.9‰and2.1‰,respectively,ofthesamplesbeingtested.2/230withLKM-1and2/230withSLA/LPwereseeninindividualsinfectedwithAIHandHCV,respectively.AllpatientswithPBCshowedAMAandM2antibodies.NospecificANApatternwasseeninAIHby1/Fbutanti-actinwasonlyfoundinpatientswithAIH.InNonA-Egroup,fourcaseswerepositiveofAMAandM2;threehadhightiterofSMAandother4hadSS-A,SS-BordsDNAantibodies,etc.Itwasconcludedthatthedetectionofanti-fiverantigens,ANAprofileandAMAsubtypeswerehelpfulforthediagnosisofautoimmunefiverdiseasesandoverlapsyndromes.InpatientswithNonA-Ehepatitis,thediagnosisofPBCorAIHshouldbetakenintoconsideration.
简介:AIM:Toevaluatethecorrelationofshearwaveelastography(SWE)resultswithliverfibrosishistologyandquantitativefunctionreserve.METHODS:Weeklysubcutaneousinjectionof60%carbontetrachloride(1.5mL/kg)wasgivento12caninesfor24wktoinduceexperimentalliverfibrosis,witholiveoilgivento2controlcanines.At24wk,liverconditionwasevaluatedusingclinicalbiochemistryassays,SWEimaging,lidocainemetabolitemonoethylglycine-xylidide(MEGX)test,andhistologicfibrosisgrading.Clinicalbiochemistryassayswereperformedattheinstitutionalcentrallaboratoryforroutineliverfunctionevaluation.Liverstiffnesswasmeasuredintriplicatefromthreedifferentintercostalspacesandexpressedasmeanliverstiffnessmodulus(LSM).PlasmaconcentrationsoflidocaineanditsmetaboliteMEGXweredeterminedusinghigh-performanceliquidchromatographyrepeatedinduplicate.Liverbiopsysampleswerefixedin10%formaldehyde,andliverfibrosiswasgradedusingthemodifiedhistologicalactivityindexKnodellscore(F0-F4).Correlationsamonghistologicgrading,LSM,andMEGXmeasureswereanalyzedwiththePearsonlinearcorrelationcoefficient.RESULTS:At24wkliverfibrosishistologicgradingwasasfollows:F0,n=2(control);F1,n=0;F2,n=3;F3,n=7;andF4,n=2.SWELSMwaspositivelycorrelatedwithhistologicgrading(r=0.835,P<0.001).Specifically,theF4grouphadasignificantlyhigherelasticmodulusthantheF3,F2,andF0groups(P=0.002,P=0.003,andP=0.006,respectively),andtheF3groupalsohadasignificantlyhighermodulusthanthecontrolF0group(P=0.039).LSMwasnegativelyassociatedwithplasmaMEGXconcentrationsat30min(r=-0.642;P=0.013)and60min(r=-0.651;P=0.012),timeto?ofthemaximumconcentration(r=-0.538;P=0.047),andtheareaunderthecurve(r=-0.636;P=0.014).Multiplecomparisonsshowedidenticaldifferencesinthesethreemeasures:significantlylowerwithF4(P=0.037)andF3(P=0.032)ascomparedtoF0a
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简介:TheJanuskinase-signaltransducersandactivatorsoftranscription(JAK-STAT)signalingpathway,activatedbymorethan50cytokinesorgrowthfactors,playscriticalrolesinawidevarietyofcellularfunctionsinthehematopoietic,immune,neuronalandhepaticsystems.Intheliver,thissignalingpathway,activatedbymorethan20cytokines,growthfactors,hormones,andhepatitisviralproteins,playscriticalrolesinantiviraldefense,acutephaseresponse,hepaticinjury,repair,inflammation,transformation,andhepatitis.ThisarticlereviewsthebiologicalsignificanceofSTAT1,2,3,4,5,6inhepaticfunctionsanddiseases.Cellular&MolecularImmunology.2005;2(2):92-100.
简介:AccordingtoGLOBOCAN2012,livercanceristhesixthmostcommoncancerintheworld.Therewere782,000newcasesdiagnosedin2012,with50%inChinaalone.Livercanceristhesecondmostcommoncauseofcancerdeathworldwideanditsprognosisisverypoor.TheWorldHealthOrganization(WHO)declared745,517deathscausedbylivercancerin2012,withmorethanhalffromChina~1.
简介:Weprovideaconcisereviewofthemainepidemiologicalliteratureonfattyliver(FL)publishedbetweenJanuary2011andOctober2013.Thefindingsfromtheliteraturewillbeconsideredinlightofthealreadyavailableknowledge.WediscussthelimitationsinherentinthecategorizationofFLintonon-alcoholicandalcoholicFL,thepotentialrelevanceofFLasanindependentpredictorofcardiometabolicdisease,andrecentresearchaddressingtheroleofFLasanindependentpredictorofmortality.ThisreviewisorganizedasaseriesofanswerstorelevantquestionsabouttheepidemiologyofFL.
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简介:肝疾病包含许多肝条件,包括肝失败,肝肝硬化和尖锐、长期的肝炎的一个系列,例如酒鬼,丰满,药,病毒、长期的肝炎。肝损害是在肝疾病的一个主要原因的因素;通常,这些因素包括直接的肝损坏和调停免疫者的肝损害。Neutrophils(也作为neutrophilicgranulocytes或polymorphonuclear白血球(PMN)知道)是在人的最丰富的传播的白血房间类型,并且PMN是一个主要天生的有免疫力的房间子集。到微脉管系统的neutrophils的不恰当的激活和homing贡献肝疾病的许多类型的病理学的表明。这评论总结基于临床的电流和动物模型研究的嗜中性调停肝损害的新奇概念。
简介:AbstractIntestinal homeostasis depends on complex interactions between the gut microbiota and host immune system. Emerging evidence indicates that the intestinal microbiota is a key player in autoimmune liver disease (AILD). Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and IgG4-related sclerosing cholangitis have been linked to gut dysbiosis. Diverse mechanisms contribute to disturbances in intestinal homeostasis in AILD. Bacterial translocation and molecular mimicry can lead to hepatic inflammation and immune activation. Additionally, the gut and liver are continuously exposed to microbial metabolic products, mediating variable effects on liver immune pathologies. Importantly, microbiota-specific or associated immune responses, either hepatic or systemic, are abnormal in AILD. Comprehensive knowledge about host-microbiota interactions, included but not limited to this review, facilitates novel clinical practice from a microbiome-based perspective. However, many challenges and controversies remain in the microbiota field of AILD, and there is an urgent need for future investigations.
简介:Livertransplantation(LT)isalife-savingtreatmentforpatientswithend-stageliverdiseaseandforpatientswithlivercellcancerrelatedtoliverdisease.Acuteandchronicliverdiseasesrelatedtohepatitisvirusesarebetweenthemainindicationsforlivertransplantation.Theriskofviralreinfectionaftertransplantationisthemainlimitingfactorintheseindications.Beforetheavailabilityofantiviralprophylaxis,hepatitisBvirus(HBV)recurrencewasuniversalinpatientswhowereHBVDNA-positivebeforetransplantation.ThenaturalhistoryofrecurrentHBVwasacceleratedbyimmunosuppression,anditprogressedrapidlytograftfailureanddeath.Introductionofpost-transplantprophylaxiswithimmunoglobulinalonefirst,andassociatedtoantiviraldrugslater,drasticallyreducedHBVrecurrence,resultinginexcellentlong-termoutcomes.Onthecontrary,recurrenceofhepatitisCisthemaincauseofgraftlossinmosttransplantprograms.Overall,patientandgraftsurvivalafterLTforhepatitisCvirus(HCV)-associatedcirrhosisisinferiorcomparedwithotherindications.However,successfulpretransplantorposttransplantantiviraltherapyhasbeenassociatedwithincreasedgraftandoverallsurvival.Untilrecently,thecombinationofpegylatedinterferonandribavirinwasthestandardofcareforthetreatmentofpatientswithchronichepatitisC.Highlyactiveantiviralcompoundshavebeendevelopedoverthepastdecade,thankstonewinvitrosystemstostudyHCVentry,replication,assembly,andrelease.
简介:AbstractIt has been reported that liver fibrosis could be reversed after eliminating liver injuries. This article systematically summarizes the evidence of fibrosis regression based on histology, liver stiffness, and serum biomarkers, and discusses several clinically relevant challenges. Evidence from liver biopsy has been regarded as the gold standard in the assessment of fibrosis regression. Semi-quantitative staging and grading systems are traditionally and routinely used to define regression. Recently, the predominantly regressive, indeterminate, and predominantly progressive score was proposed, based on the regressive features from "hepatic repair complex" , to provide additional information regarding the quality of fibrosis. For non-invasive assessment, although liver stiffness and serum biomarkers could be applied to reflect the dynamic changes of liver fibrosis, other confounding factors such as liver inflammation have to be considered. In conclusion, both histology and non-invasive methods can provide evidence regarding fibrosis regression. The predictive value of fibrosis regression in long-term prognosis warrants further investigation.
简介:AIM:ToinvestigatehowweightgainafterOLTaffectsthespeedoffibrosisprogression(SFP)duringrecurrenthepatitisCvirus(HCV)infectionofthegraft.METHODS:Ninetyconsecutivepatients(63males,medianage53years;55withHCV-relatedliverdisease),transplantedatasingleinstitution,werestudied.Allwerefollowedforatleast2yearsafterOLTandhadatleastonefollow-upgraftbiopsy,performednotearlierthan1yearafterthetransplantoperation.Foreachbiopsy,asingle,experiencedpathologistgaveanestimateofboththestagingaccordingtoIshakandthedegreeofhepaticsteatosis.TheSFPwasquantifiedinfibrosisunits/month(FU/mo).Thelipidmetabolismstatusofpatientswassummarizedbytheplasmatriglycerides/cholesterol(T/C)ratio.Bodymassindex(BMI)wasmeasuredbeforeOLT,and1and2yearsafterit.RESULTS:IntheHCVpositivegroup,thehighestSFPwasobservedinthefirstpost-OLTyear.Atthattimepoint,aSFP≤0.100FU/mowasobservedmorefrequentlyamongrecipientswhohadreceivedtheirgraftfromayoungdonorandhadapre-transplantBMIvalue>26.0kg/m2.Atcompletionofthefirstpost-transplantyear,aBMIvalue>26.5kg/m2wasassociatedwithaT/Cratio≤1.TheproportionofpatientswithSFP>0.100FU/modescendedinthefollowingorder:femalerecipientswithahighT/Cratio,malerecipientswithhighT/Cratio,andrecipientsofeithergenderwithlowT/Cratio.Hepaticsteatosiswasobservedmorefrequentlyinrecipientswho,inthefirstpost-transplantyear,hadincreasedtheirBMI≥1.5kg/m2incomparisontothepre-transplantvalue.Hepaticsteatosiswasinverselyassociatedwiththestagingscore.CONCLUSION:AmongHCVpositiverecipients,excessweightgainpost-OLTdoesnotrepresentafactorfavoringearlyliverfibrosisdevelopmentandmightevenbeprotectiveagainstit.
简介:PhyllanthusUrinariaL.(PUL)isatraditionalChinesemedicineusedtotreathepaticandrenaldisorders.However,themechanismofitshepatoprotectiveactionisnotfullyunderstood.Inthepresentstudy,bloodbiochemicalindexesandliverhistopathologicalchangeswereusedtoestimatetheextentofhepaticinjury.GC/MSandLC/MS-baseduntargetedmetabolomicswereusedincombinationtocharacterizethepotentialbiomarkersassociatedwiththeprotectiveactivityofPULagainstCCl_4-inducedliverinjuryinrats.PULtreatmentcouldreversetheincreaseinALT,ASTandALPinducedbyCCl_4andattenuatethepathologicalchangesinratliver.SignificantchangesinlivermetabolicprofilingwereobservedinPUL-treatedgroupcomparedwithliverinjurymodelgroup.SeventeenbiomarkersrelatedtothehepatoprotectiveeffectsofPULagainstCCl_4-inducedliverinjurywerescreenedoutusingnonparametrictestandPearson'scorrelationanalysis(OPLS-DA).TheresultssuggestedthatthepotentialhepatoprotectiveeffectsofPULinattenuatingCCl_4-inducedhepatotoxicitycouldbepartiallyattributedtoregulatingL-carnitine,taurocholicacid,andaminoacidsmetabolism,whichmaybecomepromisingtargetsfortreatmentoflivertoxicity.Inconclusion,thisstudyprovidesnewinsightsintothemechanismofthehepatoprotectionofPhyllanthusUrinaria.
简介:YoungWistarratsweredividedintosixgroups,theexperimentalgroupsweregivenLa(NO3)3atdoseof20,10,2,0.2,0.1mg*kg-1andthecontrolgroupwasgivenphysiologicalsalinerespectivelyforsixmonths.Theanimalswereweighedandtheratiosofthelivertobodyweightwerecounted.Pathologicalchangesofliverwereobservedbylightmicroscopeandtransmissionelectronmicroscope.Glutamic-oxalacetictransaminase(GOT),glutamic-pyruvictransaminase(GPT),gamma-glutamyltransferase(γ-GT)andalklinephosphatase(ALP)intheserumweremeasured.Theresultsindicatethatthebodyweightofanimalsgainesslowlyinthegroupof20mg*kg-1La(NO3)3,butitgainedquicklyintheratsfedwith0.1mg*kg-1La(NO3)3.Biochemicalindexeshavenoabnormalchanges.Inthegroupof20mg*kg-1La(NO3)3,therewerelipiddropletsanddecreaseofglycogeninthehepatocytes,densermatrixofthemitochondria,deformationofthenucleiofsomehepatocytestodifferentdegreeandinfiltrationofinflammatorycellsatportalarea.ThemorethedoseofLa(NO3)3weregiventotherats,themorethenumberofbodiescontaininghighlyelectronicdensegravel-likegranulesandthesecondarylysosomeswithdensebodies.Theratsfedwith20mg*kg-1La(NO3)3forsixmonthsshowsinjuriouseffectsonthehepatocytes.
简介:Alcoholicliverdiseaseisanestablished,yetcontroversial,indicationforlivertransplantation.Althoughanabstinenceperiodofupto6mopriortotransplantationismandatory,alcoholrelapseaftertransplantationisacommonevent.Incaseofrecurrenceofheavydrinking,graftsurvivalissignificantlyimpaired.Guidelinesondetectionandsurveillanceofalcoholconsumptioninthispatientcohortarelacking.Thisreviewsummarizesthechallengeofpatientselectionaswellasthecurrentknowledgeonestablishedandnovelalcoholbiomarkerswithspecialfocusonlivertransplantcandidatesandrecipients.