内科学-肝硬化-张顺财

HepaticCirrhosis,ProfessorWangJi-yao,ZhangShuncaiDepartmentofInternalMedicineDivisionofGastroenterology,Zhongshanhospital,FuDanuniversity.,Cirrhosis-definition,chronic,progressed,diffusehepatocellularinjuryfibrosisnodularregenerationIncidence:17/100000/yAge:20-50yr.,Hepaticcirrhosis,Etiology,LiverfunctionInjury,Portalhypertension,Diffuse,chronicliverinjury,Hepato-cellularnecrosis,collapseofhepaticlobules,regenerativenodulesformation,Formationofdiffusefibroussepta,Complations:UpperGIBleeding,Hepaticcoma,infections,primarylivercancer,Functionalrenalfailure,1.Chronicviralhepatitis(慢性病毒性肝炎):HBV,HCV,HBV+HDV2.Long-termalcoholism(慢性酒精中毒)80g/d,10yr.3.Prolongedcholestasis(长期胆汁郁积),intra-andextra-hepatic:primarybiliarycirrhosis,PBC/secondarybiliarycirrhosis4.Drugsandtoxins(药物和毒物)toxichepatitis-chronicactivehepatitis-cirrhosis5.Nonalcoholicsteatohepatitis(NASH)(非酒精性脂肪性肝炎),Etiologyofcirrhosis(I),Etiologyofcirrhosis(II),6.Hepaticvenousoutflowobstruction(肝血液循环障碍)veno-occlusivedisease,Budd-Chiarisyndrome,constrictivepericarditis7.Metabolicdisorders(遗传代谢性疾病)hemochromatosis(血色病);Wilsonsdisease(肝豆状核变性);8.Autoimmunehepatitis(AIH)(自身免疫性肝炎)9.Schistosomiasis(血吸虫病)10.Cryptogenic(隐原性)11.Mixed:alcohol+virus,HBV+HCV,HBV+schistosomiasis,Hepaticstellatecellactivation,Liverfibrosis,accumulationofextracellularmatrixinliver,synthesisofmatrixproteins,degradationofmatrixproteins,CollagenstypeIandIIIconstitutemorethan95%ofthetotalcontentofincreasedcollageninfibroticliver,Pathogenesis:chronic,progressed,diffuse,Hepatocyteinjuryleadingtonecrosis.Chronicinflammation-(hepatitis).Capillarization(肝窦毛细血管化)ofthespaceofDisseisakeyevent.Bridgingfibrosis.Regenerationofremaininghepatocytesproliferateasroundnodulessurroundedbyfibroussepta.Lossofvasculararrangementresultsinregeneratinghepatocytesineffective.Cirrhosismayleadtoliverfailure,portalhypertension,ordevelopmentofhepatocellularcarcinoma,Histopathologicclassification,micronodularuniformlysmallnodules(250neutrophils/mm3.,ComplicationsII,Hepatocellularcarcinoma(肝细胞肝癌)Hepaticencephalopathy(肝性脑病)Asterixis(扑翼样振颤)Disoriented(定向障碍)Coma(昏迷),ComplicationsIII,Hepatorenalsyndrome(HRS):Oliguria(少尿),azotemia(氮质血症),hypotension(低血压),dilutionalhyponatremia(稀释性低钠血症),lowurinarysodium(低钠尿),ComplicationsIV,Electrolyteandacid-baseimbalance(电介质酸硷平衡失调)hyponatremia,hypokalemiaAndhypochloremicalkalosis,LaboratoryfindingsI,BloodandurineroutinesLiverfunctiontests-toestimatetheseverityofliverdysfunction：ALT,AST,AKP,GGT,serumtotalbilirubin,serumalbumin,prothrombintime,globulin,cholesterol.-todifferentialdiagnosis:Alcoholic:AST/ALT=2;PBC:AKP,GGTALT,AST-torefecthepaticfibrosis:PIIIP、HA、laminin-toquanlityliverfunction,Immunology,Cellularimmune,hormonalimmuneautoimmuneliverdisease:IgG,globulinANA(+),SMA(+)PBC:IgM,AMA(+)MarkerofvirusAFP,LaboratoryfindingsII,Ascitesparacentesis:routine,culture,ADA,LDH,SAAG(serumascitesalbumingradient)(血清腹水白蛋白梯度)11g/LUltrasonography,CTscanning：biliaryobstruction,livermasses,splenomegaly,ascites.Endoscopy:thenumber,appearance,andsizeofanyesophageal/gastricvarix,portalhypertensivegastropathy(PHG),LaboratoryfindingsIII,Radionuclide:99mTC-MIBI,H/Lliverbiopsy:toconfirmthediagnosisLaparoscopyHVPG(hepaticveinpressuregradient)(肝静脉压力梯度)(wedged-free)hepaticvenouspressureNormal:5-6mmHg,10mmHg:varices;12mmHg:rupture,DiagnosisI,EtiologyofcirrhosisPathologyofcirrhosisEvaluatingofliverfunction:Child-PughclassificationSearchingforcomplications,DiagnosisII,thehistoryofdiseasecontributestoidentifyingthecauseofcirrhosis.historyofviralhepatitis,bloodtransfusions,medicationuse,alcoholuse,sexualpracticesshouldbecarefullyreviewed.signsandsymptomsconfirmtoexistenceofportalhypertensionandimparedliverfunction.liverfunctiontests:hypoalbuminemia,hyperbilirubinemia，theprolongedprothrombintimesuggesthepaticdecompensation.Imagingstudy:UltrasoundandCTreadilyidentifythelesion,buthavenocharacteristicfindings.,Child-PughclassificationScoreavariable123Encephalopathy(degree)NilSlight-ModerateModerate-SevereAscites(degree)NilSlightModerate-SevereBilirubin(umol/L)51Albumin(g/L)3528-347040-7018ProthrombinTime(INR)1.5*PBC:SB(mol/L)176868170170aScoresaresummedtodetermineChildsclass:classA=5-6classB=7-9classC=10-15,DiagnosisIII,DifferentialDiagnosis,Otherconditionofhepatomegalyorsplenomegaly：chronicvirushepatitis,Gauchersdisease,lymphomasandleukaemias,congestivesplenomegalyDifferebtialdiagnosisofcirrhoticascitesandothertypesofascites：malignantascites,constrictivepericarditis,tuberculousperitonitis,etal.Portalhypertension:,TreatmentofcirrhosisI,specifictreatmentfortheunderlyingetiologyoftheliverdiseaseantivirustherapy-viralhepatitisabstinencefromalcohol-alcoholicUrsodeoxycholicacid(UDCA)(熊去氧胆酸)-PBCPenicillamine(青霉胺)WilsonsdiseaseGeneralTreatments:Highcalories(40kcal/kgd)、adequateprotein(1-1.5g/kgd)、vitamin、Herbalcompounds.,TreatmentofAscites,a.Bedrest,sodiumandwaterrestriction.1.Fluidintake:800-1000ml/d(hyponatremia,serumsodium1Spironolactone(安体舒通)+furosemide(速尿)urinarysodium/urinarypotassium1higherdosesspironolactone，,TreatmentofAscites(III),c.Large-volumeparacentesisassociatedwithplasmavolumeexpansiond.Ascitesultrafiltrationandre-infusione.Peritoneo-venous(LeVeen)shuntsf.TIPS(transjugularintrahepaticporto-systemicstent)(经颈静脉门体分流术)g.Livertransplantation(肝移植),TIPS-stentpositionedbetweenthehepaticandportalveins,TreatmentofcirrhosisIV,surgicaltreatmentofportalhypertensionportacavalshuntsurgery：portacavalmesocavaldistalsplenorenalshuntsChoiceofpatients：Child-Pugh:A,Bbleedingfromgastroesophagealvarices,hypersplenism.,TreatmentofcirrhosisV,TreatmentcomplationsTreatmentofacutevaricealhaemorrhage：-Generalmanagement:abstainfood,intensivecare,volumeandbloodreplacement,specificmeasurestostopthebleeding-Pharmacologicaltherapy:vasopressin(垂体后叶素)somatostatin(生长抑素)Octreotide(奥曲肽),Treatmentofacutevaricealhaemorrhage：,_Emergentendoscopy:afterPatientshemodynamicstatusstabilized(usuallywithin2-12hours)-Balloontubetamponade(ifbleedingcontinues)-Endoscopicvaricealsclerotherapyandbandligation-Prophylactictherapytopreventrebleeding:Beta-adrenergicantagonists(普奈洛尔),endoscopicsclerotherapy(硬化剂)/banding(套扎)(usually3-6sessions),portacavalshunting,TIPS,TIPS-stentpositionedbetweenthehepaticandportalveins,Treatment,portalhypertension(250/mm3:antibiotictherapyshouldbeinitiated.2.AscitesPMN250/mm3andasciticfluidculturecontinuestobepositive:initiationofantibiotictreatment.3.Follow-updiagnosticparacentesisperformed48hoursafterstartingtherapyallowsassessmentofresponsetotreatmentandtheneedtomodifyantibioticcoverage.4.Long-termprophylaxis-PatientswhohaverecoveredfromanepisodeofSBPareatahighriskofdevelopingSBPrecurrence.,TherapiesforHRSI,Avoiduseofnephrotoxicdrugs:（1）Antibiotics：aminoglycosides（2）NSAIDs：inhibitformationintrarenalprostaglandins-markeddeclineinrenalfunctionAvoidandtreatfactorstohypovolaemia:（1）activetreatmentsofuppergastrointestinalbleeding（2）Judicioususeofdiuretics（weightloss0.5Kg/d）Rectifyelectrolyteandmetabolicimbalance,Fluidintakerestriction,TherapiesforHRSII,Volumeexpansion:withIVdextrose,plasma,albuminorConcomitantplasmavolumeexpansionwithalbuminhasbeen