Liver cirrhosis 렉쳐 2007180026 김호연

8/6/2019 Liver cirrhosis 2007180026

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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

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Liver cirrhosis 렉쳐 2007180026 김호연