英文 肝硬化課件

HepaticCirrhosisCirrhosis---definition

chronic,progressed,diffuse

hepatocellularinjury

fibrosis

nodularregenerationIncidence:17/100000/yAge:20-50yr.Hepaticcirrhosis》EtiologyLiverfunctionInjury,PortalhypertensionDiffuse,chronicliverinjuryHepato-cellularnecrosis,collapseofhepaticlobulesregenerativenodules

formationFormationofdiffusefibrousseptaComplations:UpperGIBleeding,Hepaticcoma,infections,primarylivercancer,FunctionalrenalfailureEtiologyofcirrhosis(II)6.Hepaticvenousoutflowobstruction(肝血液循環(huán)障礙)

veno-occlusivedisease,Budd-Chiarisyndrome,constrictivepericarditis7.Metabolicdisorders

(遺傳代謝性疾病)

hemochromatosis(血色病);Wilson‘sdisease(肝豆狀核變性);8.Autoimmunehepatitis(AIH)(自身免疫性肝炎)9.Schistosomiasis(血吸蟲病)10.Cryptogenic

(隱原性)11.Mixed:alcohol+virus,HBV+HCV,HBV+schistosomiasisHepaticstellatecellactivationLiverfibrosisaccumulationofextracellularmatrixinliver

synthesisofmatrixproteinsdegradationofmatrixproteinsCollagenstypeIandIIIconstitutemorethan95%ofthetotalcontentofincreasedcollageninfibroticliver

Pathogenesis:chronic,progressed,diffuseHepatocyteinjuryleadingtonecrosis.Chronicinflammation-(hepatitis).Capillarization(肝竇毛細血管化)ofthespaceofDisseisakeyevent.Bridgingfibrosis.Regenerationofremaininghepatocytesproliferateasroundnodulessurroundedbyfibroussepta.Lossofvasculararrangementresultsinregeneratinghepatocytesineffective.Cirrhosismayleadtoliverfailure,portalhypertension,ordevelopmentofhepatocellularcarcinoma

Consequencesofportalhypertension[I]1.Splenomegaly(脾腫大)2.Formationandopenofportal-systemiccollateral’s(門體側支循環(huán)開放)

--Esophageal/gastricvarices

(食管/胃靜脈曲張)

(shortgastric/coronaryveins)

--Rectalcollateral‘s(痔靜脈叢)

(Suphemorrhoidal/middle&inf.hemorrhoidal)

--Caputmedusae(水母頭)(

umbilical/epigastric)

--abdominalwallvarices(腹壁靜脈曲張)

--PortalsystemandleftrenalConsequencesofportalhypertension[II]3.Ascites(腹水)

Theoriesofascitesformation

Underfillingtheory(灌注不足假說）

Overflowtheory(泛溢假說)Arterialvasodilationtheory(動脈擴張假說)AscitesSodiumretention

---Reninangiotensionaldosteronesystem(RAAS)---sympatheticnervesystem,norepinephrine---Intrarenalfactors:Kallikrein-kininsystem,Adenosine.Waterretention

---Antidiuretichormone(ADH)---ImpairedrenalsynthesisofPGs(PGE2)Renalvasoconstriction

---RAAS,AngiotensionII---SNS---ADH---ETPulmonarymanifestationsHepatichydrothorax

(肝性胸水)Hepatopulmonarysyndrome(HPS,肝肺綜合征)HRSischaracterizedclinicallybythetriadofpulmonaryvasculardilatationcausingarterialhypoxemiainthesettingofadvancedliverdisease.

HRS(Hepatorenalsyndrome,肝腎綜合征)

Occurredinthesettingof:---chronicliverdisease---advancedhepaticfailure---portalhypertensioncharacterizedby:

---impairedrenalfunction---markedabnormalitiesinarterialcirculation---activationofendogenousvasoactivesystemClassifiedinto2differenttypes:

---TypeI:Rapidlyprogressive---TypeII:Notrapidlyprogressive.OftenresultsinmildrenalinsufficiencycausingdiureticresistantascitesClinicalfeatures[I]Compensatedcirrhosis(代償期)

Manypeopleexperiencefewsymptomsattheonsetofcirrhosis,symptomsaretypicallyvagueandnonspecific.

---Fatigueandlossofenergy.---Lossofappetiteandnausea.---Spiderangiomas---liverfunctionisnormalDecompensatedcirrhosis(失代償)

Symptomscausedbylossoffunctioninglivercells

---System：fatigue,weakness,weightloss,malnutrition---DigestiveSystem:Lossofappetite,nausea,diarrhea.Clinicalfeatures[II]

---Tendencytohemorrhage(出血傾向)andanaemia(貧血):Duetoreducedsynthesisofcoagulationfactors(II,V,VII,IX,X),hypersplenism(脾亢),lowplateletcount,poorabsorption，gastrointestinalbleeding.---Hormonalabnormalities

gynecomastia(男性乳房發(fā)育),telangiectases(毛細血管擴張癥),spidernevi(蜘蛛痣),palmarerythema(肝掌)

---Jaundice(黃疸)Clinicalfeatures[IV]

Palpationofliverfirm,hard,irregular,enlargementroundedorsharpedgebelowtherightlowerribs.

Thespleenisoftenpalpable,andmaybeverylarge.Complications[I]Uppergastrointestinalbleeding(上消化道出血):

Hematemesis(嘔血)/melena(黑糞).Esophageal/gastricvaricealbleeding(食管/胃靜脈出血);portalhypertensivegastropathy(門脈高壓性胃病);pepticulcer(消化性潰瘍)Infections:spontaneousbacterialperitonitis(自發(fā)性細菌性腹膜炎)(4-8%)：Fever,worseningjaundiceorrenaldysfunction,abdominalpain(occurringonlyin50%ofpatients),andencephalopathyarethemostcommonclinicalfindingsinSBP.However,thepatientisfrequentlyasymptomatic.BecausecultureofascitesfluidisnegativeinalargenumberofpatientswithSBP,diagnosisshouldbebasedonthepresenceof>250neutrophils/mm3.Complications[II]Hepatocellularcarcinoma(肝細胞肝癌)Hepaticencephalopathy

(肝性腦病)Asterixis(撲翼樣振顫)Disoriented(定向障礙)Coma(昏迷)

Complications[III]

Hepatorenalsyndrome(HRS):

Oliguria(少尿),azotemia(氮質血癥),hypotension(低血壓),

dilutionalhyponatremia(稀釋性低鈉血癥),lowurinarysodium(低鈉尿)Complications[IV]Electrolyteandacid-baseimbalance(電介質酸鹼平衡失調)

hyponatremia,hypokalemiaAndhypochloremicalkalosis

Laboratoryfindings[I]BloodandurineroutinesLiverfunctiontests

---toestimatetheseverityofliverdysfunction：ALT,AST,AKP,GGT,serumtotalbilirubin,serumalbumin,prothrombintime,globulin,cholesterol.

---todifferentialdiagnosis:Alcoholic:AST/ALT>=2;PBC:AKP,GGT>>ALT,AST

---torefecthepaticfibrosis:PIIIP、HA、laminin---toquanlityliverfunctionImmunology

Cellularimmune,hormonalimmuneautoimmuneliverdisease:IgG,globulinANA(+),SMA(+)PBC:IgM,AMA(+)MarkerofvirusAFPLaboratoryfindings[II]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)Laboratoryfindings[III]

Radionuclide:99mTC-MIBI,H/L

liverbiopsy:toconfirmthediagnosisLaparoscopyHVPG(hepaticveinpressuregradient)(肝靜脈壓力梯度)(wedged-free)hepaticvenouspressureNormal:5-6mmHg,>10mmHg:varices;>12mmHg:rupture

Diagnosis[I]

EtiologyofcirrhosisPathologyofcirrhosisEvaluatingofliverfunction:Child-PughclassificationSearchingforcomplicationsDiagnosis[II]

thehistoryofdiseasecontributestoidentifyingthecauseofcirrhosis.

historyofviralhepatitis,bloodtransfusions,medicationuse,alcoholuse,sexualpracticesshouldbecarefullyreviewed.

signsandsymptomsconfirmtoexistenceofportalhypertensionandimparedliverfunction.

liverfunctiontests:hypoalbuminemia,hyperbilirubinemia，theprolongedprothrombintimesuggesthepaticdecompensation.

Imagingstudy:UltrasoundandCTreadilyidentifythelesion,buthavenocharacteristicfindings.

Child-Pughclassification

Scorea

variable

123Encephalopathy(degree)NilSlight-ModerateModerate-SevereAscites(degree)NilSlightModerate-SevereBilirubin(umol/L)<3434-51>51Albumin(g/L)3528-34<28ProthrombinIndex(%)>7040-70<40ProthrombinTime(s)<1415-17>18ProthrombinTime(INR)

<1.31.3～1.5

>1.5*PBC:SB(μmol/L)17～6868～170>170

aScoresaresummedtodetermineChild’sclass:classA=5-6classB=7-9classC=10-15Diagnosis[III]DifferentialDiagnosis

Otherconditionofhepatomegalyorsplenomegaly：

chronicvirushepatitis,Gaucher’sdisease,lymphomasandleukaemias,congestivesplenomegalyDifferebtialdiagnosisofcirrhoticascitesandothertypesofascites：

malignantascites,constrictivepericarditis,tuberculousperitonitis,etal.Portalhypertension:Treatmentofcirrhosis[I]specifictreatmentfortheunderlyingetiologyoftheliverdisease

antivirustherapy--viralhepatitisabstinencefromalcohol--alcoholicUrsodeoxycholicacid(UDCA)(熊去氧膽酸)--PBCPenicillamine(青霉胺)—Wilson’sdisease

GeneralTreatments:

Highcalories(40kcal/kg·d)、adequateprotein(1-1.5g/kg·d)、vitamin、Herbalcompounds.TreatmentofAscitesa.Bedrest,sodium

andwaterrestriction.

1.Fluidintake:800-1000ml/d(hyponatremia,serumsodium<130meq/L)2.Dietarysodiumintake

：88mmol/d(2.0gNacl)Mildpatients：restonbed，withdietarysaltrestriction,lossofascitesoccursin10%to15%ofpatients.TreatmentofAscites[II]

b.Increasingrenalsodiumandwaterexcretion:

--Diuretics:

urinarysodium/urinarypotassium>1Spironolactone(安體舒通)+furosemide(速尿)urinarysodium/urinarypotassium<1higherdosesspironolactone，

TreatmentofAscites(III)c.Large-volumeparacentesis

associatedwithplasmavolumeexpansiond.Ascitesultrafiltrationandre-infusione.Peritoneo-venous(LeVeen)shuntsf.

TIPS(transjugularintrahepaticporto-systemicstent)(經頸靜脈門體分流術)

g.Livertransplantation(肝移植)TIPS---stentpositionedbetweenthehepaticandportalveinsTreatmentofcirrhosis[IV]surgicaltreatmentofportalhypertension

portacavalshuntsurgery：

portacavalmesocaval

distalsplenorenalshunts

Choiceofpatients：

Child-Pugh:A,Bbleedingfromgastroesophagealvarices,hypersplenism.Treatmentofcirrhosis[V]TreatmentcomplationsTreatmentofacutevaricealhaemorrhage：

----Generalmanagement:abstainfood,intensivecare,volumeandbloodreplacement,specificmeasurestostopthebleeding

----Pharmacologicaltherapy:

vasopressin(垂體后葉素)somatostatin(生長抑素)

Octreotide(奧曲肽)Treatmentofacutevaricealhaemorrhage：

___Emergentendoscopy:afterPatient’shemodynamicstatusstabilized(usuallywithin2-12hours)

----Balloontubetamponade(if

bleedingcontinues)

----Endoscopicvaricealsclerotherapyandbandligation

----Prophylactictherapytopreventrebleeding:Beta-adrenergicantagonists(普奈洛爾),endoscopicsclerotherapy(硬化劑)/banding(套扎)(usually3-6sessions),portacavalshunting,TIPSTIPS---stentpositionedbetweenthehepaticandportalveinsTreatmentportalhypertension(<12mmHg)EradicatevaricesLivertransplantationShuntSurgicalshuntsTIPSPharmacotherapyQ

Endoscopy:EVS,EVLDevascularizationRTreatmentofSBP1.AscitesPMN>250/mm3:antibiotictherapyshouldbeinitiated.2.AscitesPMN<250/mm3andasciticfluidculturecontinuestobepositive:initiationofantibiotictreatment.3.Follow-updiagnosticparacentesisperformed48hoursafterstartingtherapyallowsassessmentofresponsetotreatmentandtheneedtomodifyantibioticcoverage.4.Long-termprophylaxis---PatientswhohaverecoveredfromanepisodeofSBPareatahighriskofdevelopingSBPrecurrence.TherapiesforHRS[I]Avoiduseofnephrotoxicdrugs:

（1）Antibiotics：aminoglycosid