Liver cirrhosis 렉쳐 2007180026 김호연
Transcript of Liver cirrhosis 렉쳐 2007180026 김호연
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PK12
: 2011.4.4 ~ 4.15
2007180026
Liver cirrhosis
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(regenerative nodules)
,,
, . .
1)
2)
1.
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2.
HBV(50%, m/c)
Alcohol(30%)
HCV(10%)
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: B (65~75%),C (10~20%)
(10~20%)
: (hemochromatosis),
: primary biliary cirrhosis
: Budd-Chiari , membranousocclusionofIVC,
: Methotrexate,Amiodarone
2.
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3.
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2) Portalhypertension ,
(1)esophageal/gastric varix (bleeding)
(2)splenomegaly & hypersplenism
(3)ascites : edema, SBP,hepatorenal syndrome
(4)hepatic encephalopathy
3)
, ,
3.
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,, .
1) ,,,,
spiderangioma, palmarerythema,gynecomastia
2) , ,
prothrombin time
AST/ALT , bilirubin,albumin
3) US orCT : surfacenodularity,enlarged coudate lobe,regeneratingnodules
4) : or
4.
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spiderangioma palmarerythema
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gynecomastia
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liver cirrhosis,splenomegaly
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:
1) : ,, steroid
,
2) : US (AFP)
:
,
5.
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.
compensatedLC : 5YSR 90%
6 decompensatedLC , mediansurvival 9
decompensatedLC : 75% 1~5 LC , median
survival 1.5
LC : (m/c, 40%), ( 20%),,
1)Child-Turcotte-Pugh(CTP)score
2) MELDscore
6.
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1) Child-Turcotte-Pugh (CTP) score
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2) MELD score
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1)Definition
Excessive chronic alcoholuse can causeseveraldifferenttypesofchronicliverdisease,includingalcoholic fattyliver,alcoholic hepatitis,andalcoholiccirrhosis
Chronic alcoholuse can producefibrosisintheabsenceofaccompanyinginflammationand/ornecrosis
2) Pathology & pathogenesis
Fibrosis can be centrilobular, pericellular,or periportal. Whenfibrosisreachesa certaindegree,thereisdisruptionofthenormalliverarchitectureandreplacementofliver cells byregenerativenodules
Inalcoholic cirrhosis,thenodulesareusually
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Withacetaldehyde-mediatedhepatocytedamage, certainreactiveoxygenspecies canresultinKupffer cellactivation.
profibrogenic cytokinesare producedthatinitiateand perpetuatestellatecellactivation, withtheresultant productionofexcesscollagen and
extracellular matrix.
Connectivetissueappearsin bothperiportal andpericentral zonesandeventually connects portaltriads with centralveinsformingregenerativenodules.
Hepatocytelossoccurs,and withincreased collagen productionand
deposition,together with continuinghepatocytedestruction,theliver
contractsandshrinksinsize
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3)Clinical manifestations
Patients withalcoholic liverdiseasecan present withnonspecific symptomssuchasvaguerightupper quadrant pain,fever,nauseaandvomiting,diarrhea,anorexia,andmalaise
Alternatively,they may present with morespecific complicationsofchronicliverdisease,includingascites,edema,oruppergastrointestinal(GI)hemorrhage
Other clinical manifestationsincludethedevelopmentofjaundiceorencephalopathy
physicalexamination,theliverandspleen may beenlarged, withtheliver
edge beingfirm andnodular frequentfindingsincludescleralicterus,palmarerythema,spiderangiomas,
parotidglandenlargement,digital clubbing, muscle wasting,orthedevelopmentofedemaandascites
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4)Lab findings
Laboratorytests may be completelynormal in patients withearlycompensatedalcoholic cirrhosis
Patients may beanemic eitherfrom chronic GI bloodloss,nutritional
deficiencies,orhypersplenism relatedtoportalhypertension,orasadirectsuppressiveeffectofalcoholonthe bone marrow
Platelet countsareoftenreducedearlyinthedisease,reflectiveofportalhypertension withhypersplenism
Serum total bilirubin can benormalorelevatedwithadvanceddisease.
Prothrombin timesareoften prolongedandusuallydonotrespondto
administrationofparenteralvitamin K Serum aminotransferases(ALT,AST)aretypicallyelevated, particularlyin
patients who continuetodrink, withAST levels beinghigherthanALT levels,usually bya2:1 ratio.
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5)Diagnosis
Thediagnosis ofalcoholic liverdiseaserequiresanaccuratehistoryregarding bothamountanddurationofalcohol consumption
Patients whohaveanyoftheabove-mentioned clinicalfeatures, physical
examinationfindings,orlaboratorystudiesshould be consideredtohavealcoholic liverdisease
6) Treatment
Abstinenceisthe cornerstoneoftherapyfor patients withalcoholic liverdisease
Inaddition, patientsrequiregoodnutritionandlong-term medical
supervisioninorderto manageunderlying complicationsthat maydevelop
Glucocorticoids areoccasionallyusedin patients withseverealcoholichepatitisintheabsenceofinfection
Othertherapiesthathave beenusedincludeoralpentoxifylline, whichdecreasesthe productionoftumornecrosisfactor(TNF-)andotherproinflammatory cytokines
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OfpatientsexposedtothehepatitisCvirus(HCV),approximately80%develop chronic hepatitisC,andofthose,about2030% willdevelopcirrhosisover 2030 years
OfpatientsexposedtohepatitisB,about5% develop chronic hepatitisB,
andabout20% ofthose patients willgoontodevelop cirrhosis Patients with cirrhosisduetoeither chronic hepatitisCorB can present
withtheusualsymptomsandsignsofchronic liverdisease
Diagnosisrequiresathoroughlaboratoryevaluation,includingquantitativeHCV RNAtestingandanalysisforHCVgenotype,or
hepatitisBserologies toincludeHBsAg,anti-HBs,HBeAg (hepatitisBeantigen),anti-HBe,and quantitativeHBVDNAlevels
Cirrhosis due to chronic viral hepatitis
B or C
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In patients withchronic hepatitisB,numerousstudieshaveshownbeneficialeffectsofantiviraltherapy, whichiseffectiveatviralsuppression,asevidenced byreducingaminotransferaselevelsandHBVDNAlevels,andimprovinghistology byreducinginflammationand
fibrosis. Several clinicaltrialsand caseserieshavedemonstratedthatpatients withdecompensatedliverdisease can become compensatedwiththeuseofantiviraltherapydirectedagainsthepatitisB. Currentlyavailabletherapyincludeslamivudine,adefovir,entecavir,andtenofovir.Interferon- canalso beusedfortreatinghepatitisB, butitshouldnotbeusedin cirrhotics.
Treatmentofpatients with cirrhosisduetohepatitisC isalittle moredifficultbecausethesideeffectsofpegylated interferonandribavirintherapyareoftentimesdifficultto managein patients with cirrhosis
Nonetheless,ifpatients cantoleratetreatment,andifitissuccessful,thebenefitisgreatanddisease progressionisreduced.
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Other causesofposthepatitic cirrhosisincludeautoimmunehepatitisand cirrhosisduetononalcoholic steatohepatitis
Many patients withautoimmunehepatitis(AIH)present with cirrhosisthatisalreadyestablished. Typically,these patientswillnot benefitfrom
immunosuppressivetherapy withglucocorticoidsorazathioprinesincetheAIHis "burnedout.
Diagnosisinthissettingrequires positiveautoimmune markerssuchasantinuclearantibody(ANA)oranti-smooth-muscleantibody(ASMA).
When patients withAIH present withcirrhosisandactiveinflammation
accompanied byelevatedliverenzymes,there can be considerablebenefitfrom theuseofimmunosuppressivetherapy.
Managementofcomplicationsofcirrhosis duetoeitherAIHornonalcoholic steatohepatitis issimilar tothatforotherformsofcirrhosis.
Cirrhosis from autoimmune hepatitis
and nonalcoholic fatty liver disease
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Biliary cirrhosis fibrosis cirrhosis .
Biliary cirrhosishas pathologic featuresthataredifferentfrom eitheralcoholic cirrhosisor posthepatitic cirrhosis,yetthe manifestationsofend-stageliverdiseasearethesame
Cholestatic liverdisease mayresultfrom necroinflammatory lesions,congenitalor metabolic processes,orexternal bileduct compression
The major causesofchronic cholestatic syndromesare primary biliarycirrhosis(PBC),autoimmune cholangitis, primarysclerosing cholangitis(PSC),andidiopathic adulthoodductopenia
theyallsharethehistopathologic featuresofchronic cholestasis,suchascholate stasis, copperdeposition,xanthomatous transformationofhepatocytes,andirregularso-called biliaryfibrosis
there may be chronic portalinflammation,interfaceactivity,and chroniclobularinflammation
Biliary cirrhosis
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1) Pathology
Itis characterized byportalinflammationandnecrosisofcholangiocytes insmalland medium-sized bileducts
bileduct cholestasis, cirrhosis .
2)Clinical manifestations most patientsareactuallyasymptomatic
Whensymptomsare present,they most prominentlyincludeasignificantde
greeoffatigue outofproportionto what would beexpectedforeithertheseverityoftheliverdiseaseortheageofthe patient
Pruritus isseeninapproximately 50% ofpatientsatthetimeofdiagnosis
Physicalexamination canshowjaundice andother complicationsofchronic l
iverdiseaseincludinghepatomegaly,splenomegaly,ascites,andedema
PBCincludehyperpigmentation,xanthelasma,andxanthomata, whicharer
elatedtothealtered cholesterol metabolism seeninthisdisease
Primary biliary cirrhosis
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3)Lab findings
Laboratoryfindingsin PBCshow cholestatic liverenzymeabnormalitieswit
hanelevationin-glutamyl transpeptidase andalkaline phosphatase (ALP)along with mildelevationsinaminotransferases (ALT andAST).
Immunoglobulins,
particularlyIgM,aretypicallyincreased
Hyperbilirubinemia usuallyisseenonce cirrhosishasdeveloped
Thrombocytopenia,leukopenia,andanemia may beseenin patients with portalhypertensionandhypersplenism
4)Diagnosis
PBCshould be consideredin patients with chronic cholestatic liverenzymeabnormalities. Itis mostoftenseeninmiddle-aged women
Antimitochondrial antibodies(AMA)are presentinabout90% ofpatients with PBC
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5) Treatment
Treatmentofthetypical manifestationsofcirrhosisarenodifferentfor PBCthanforotherformsofcirrhosis
UDCA has beenshowntoimprove both biochemicalandhistologic features
ofthedisease UDCAhas beenshowntoslow therateofprogressionofPBC, butitdoesno
treverseor curethedisease
Certain patients mayneedto be consideredforlivertransplantation shouldt
heirliverdiseasedecompensate.
The mainsymptomsofPBCarefatigue andpruritus,andsymptom manage
mentisimportant Pruritus istreated withantihistamines,narcotic receptorantagonists(naltre
xone),andrifampin
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1)Definition
PSCisa chronic cholestatic syndromethatis characterized bydiffuseinflammationandfibrosisinvolvingtheentire biliarytree,resultinginchronic cholestasis
This pathologic processultimatelyresultsinobliteration ofboththeintra-andextrahepatic biliarytree,leadingtobiliary cirrhosis, portalhypertension,andliverfailure
2)Clinical manifestations
Theusual clinicalfeaturesofPSCarethosefoundincholestatic liverdisease,
withfatigue, pruritus,steatorrhea,deficienciesoffat-solublevitamins,and
theassociated consequences
Primary sclerosing cholangitis
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3)Lab findings
Patients with PSCtypicallyareidentifiedinthe courseofanevaluationofabnormalliverenzymes
Most patientshaveatleastatwofoldincreaseinALP and mayhaveelevated
aminotransferases as well Albuminlevels may bedecreased,andprothrombin timesare prolongedina
substantial proportionofpatientsatthetimeofdiagnosis
theperinuclear antineutrophil cytoplasmic antibody(P-ANCA)is positiveinabout 65% ofpatients with PSC
4)Diagnosis
ThedefinitivediagnosisofPSCrequires cholangiographic imaging
MRI with magnetic resonance cholangiopancreatography (MRCP)has beenutilizedastheimagingtechniqueofchoiceforinitialevaluation.
someinvestigatorsfeelthatendoscopic retrogradecholangiopancreatography (ERCP)shouldalso be performedto be certain
whetherornotadominantstrictureis present
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Typical cholangiographic findingsin PSCaremultifocalstricturing andbeading involving boththeintrahepatic andextrahepatic biliarytree
5) Treatment
Thereisnospecific proventreatmentfor PSC,althoughstudiesare currently
ongoingusinghigh-dose (20 mg/kg perday)UDCA
todetermineits benefit Endoscopic dilatationofdominantstrictures can behelpful, buttheultimate
treatmentislivertransplantation
Adreaded complicationofPSCisthedevelopmentofcholangiocarcinoma,
whichisarelativecontraindicationtolivertransplantation
Symptomsofpruritusare common,andtheapproachisas mentioned
previouslyforthis problem in patients with PBC
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Harrisons PrinciplesofInternal Medicine, 17th ed.
uptodate.com
Reference