CIROZA HEPATICProf. Dr. Mircea DICULESCUCatedra de Gastroenterologie si Hepatologie Fundeni

DEFINIIEFIBROZAdifuz

NODULI DE REGENERARE

datorit NECROZEI HEPATOCELULARE

anatomopatologica

HIPERTENSIUNE PORTAL

plus

INSUFICIEN HEPATIOCELULARA

fiziopatologica

EPIDEMIOLOGIEPOVARA ("disease burden"):300.000 de decese pe an n lume2% din necropsii10% din alcoolici, dup 25 de ani

CGH Fundeni, anul 20011681 / 8768 internri (20%)

ETIOLOGIEVIRAL - VHB+-VHD, VHCALCOOLIC (nutriional) COLESTAZ intra & extrahepaticMETABOLIC (Wilson, hemocromatoza, glicogenoze)IMUN (LES)TOXICE (amanita phalloides, P, CCl4)staz venoas (boal veno-oclusiv, Budd Chiari, ICC, CPC, valvulopatii)BY BASSMALNUTRIIEKWASHIORKORGENETIC (grup A, HLA B8, B40, DW3)CRIPTOGENIC

PATOGENIENECROZACOLAPS LOBULARSEPTURI FIBROASEREGENERARE NODULARSTRIC ARHITECTURA LOBULARPARCELARPIECE-MEALBRIDGINGCONFLUENE

PATOGENIENODULI DE REGENERAREmping sinusoidele la periferieinsuficien circulatorie n centrul nodulilor

PATOGENIEFIBROZCELULEfibroblast - reversibil, fibrocit - ireversibilsintez FIBRE (colagen)FIBREcolagenstric arhitectura lobularFIBRONECTINA, LAMININAn membrana bazalrol chemotactic pentru fibroblast - limfokine, monokine

PATOGENIEALTE MODIFICRImodificri vasculareunturi arteriovenoase intrahepatice i sistemiceneocanalicule biliarecelule stelate (alcool)

HISTOPATOLOGIE

HISTOPATOLOGIEFICAT MACROSCOPICATROFICHIPERTROFICAMBELE FICAT MACRO - MICROSCOPICMACRONODULARMICRONODULARMIXT

CLINICA ASIMPTOMATIC = descoperire intamplatoare ( operatii, analize, necropsii)SIMPTOMATICSIMPTOME astenie, adinamie, fatigabilitate, anorexie, disconfort abdomen superiorSEMNEfebracutanat - icter, paloare, edeme, echimoze, stelue vasculare, leuconichie, Chwostek, Dupuytren, buye carminate, ginecomastie, ...locale - ficat, neregulat, dur, ascuit, - splina, - ascit..alte - TA, AV, epistaxis, infecii, malabsorbie, ...

CLINICACOMPLICAIIAscitaEncefalopatieHDS20% oligosimptomatic

PARACLINICCOLESTATICINSUFICIEN HEPATOCELULARINFLAMATORCITOLIZIMUNOLOGICHEMATOLOGICMORFOLOGIC

PARACLINICCOLESTATICbilirubin, stercobilinogen, urobilinogenfosfataza alcalin, GGT, 5 nucleotidazacolesterol totalacizi biliari

PARACLINIC2. INSUFICIEN HEPATOCELULAR proteine - albumina, fibrinogen, II, V, VII, IX, X, T Quick, transferina, ceruloplasmina, transcortina, tiroxin beta globulinaaa aromatici - liniaricolseterolaldosteron, sex-hormoniamoniogeneza, urereogenezadetoxifiereteste de traversare - BSP, roz bengal

PARACLINIC3. INFLAMATOR labilitate sericglobulineraport albumine / globulineVSHfibrinogen

PARACLINIC4. CITOLIZ aminotransferaze ALT, AST, raportul de RittisLDH, GDH, OCT, GGTsideremiederivai de acid colic

PARACLINIC5. IMUNOLOGICmarkeri virali VHB, VHD, VHChepatita autoimun si CBP - ANA, ASMA, anti LKM1, AMAimunograma IgA, IgM, IgGAFPcelule LE

PARACLINIC6. HEMATOLOGICcitopenieanemie hemolitic, feripriv, macrocitarleucocitoz

PARACLINIC7. MORFOLOGICECO - marg ascuit, noduli, desen vascular srcit n periferie, manon hiperecogen vascular, HTP - vase, splenomegaliePBHEDS - varice esogastrice, gastropatiepresiune portallaparoscopie, CT(scintigrama, splenoportografie,)

DIAGNOSTIC"Ciroz hepatic 1. atrofic / hipertrofic, 2. de etiologie ..., 3. activ / inactiv 4. compensat / decompensat portal i/sau parenchimatos5. complicat cu ...(6. tratament cu )"

DIAGNOSTIC DIFERENIALAlte cauze ale simptomelor si semnelorhepatomegaliesplenomegalieHTPHDSencefalopatie...

PROGNOSTIC5 - 6 Child A7 - 9 Child B10 - 15 Child C

= Child PUGHChild Turcott = Nutritie

PROGNOSTICFAVORABILalcool, cauz cunoscut, hipertrofic

NEFAVORABILScor Child crescut, Na+, TA

+/- FAVORABILrspuns la tratament

TRATAMENTMSURI GENERALEETIOLOGICPATOGENIC SIMPTOMATIC AL COMPLICAIILORTRANSPLANT HEPATIC

TRATAMENTMSURI GENERALErepausdiet - nu alcool, nu condimente, nu...evitare transfuziivaccinare VHA, VHB caz nu cauz

TRATAMENTETIOLOGICStop alcoolLamivudina n ciroza compensat VHBInterferon plus Ribavirina numai pentru ciroza compensat VHC (un fel de hepatit cronic care la PBH are scor Knodell de fibroz 4) - fr nici o alt modificareDesferoxamina (chelator Fe) n hemocromatozD penicilamina (chelator Cu) n boala Wilson

TRATAMENTPATOGENIC cortizon n ciroza autoimunacid ursodeoxicolic (UDCA) n ciroza biliar primitivSIMPTOMATIChepatoprotector, lipotrop, stabilizant membranarUDCA n orice ciroz 10 mg/kgcsilimarinantioxidante - vitamina Efosfolipide

TRATAMENTTRANSPLANT HEPATICpentru END STAGE LIVER DISEASE (pacientul are un prognostic infaust pe termen lung, mediu si uneori chiar scurt)list de ateptare - criterii difereniateindicaii individualizate n funcie de etiologiecomorbiditi asociateseveritate afectare hepaticcentru de transplantsistem de asigurri de sntateInstitutul Clinic Fundeni ~ 50 LTx

CONCLUZIIMAI BINE E S PREVII DECT S TRATEZIcosturi enorme, eficacitate redus a tratamentului, gref hepatic cu via limitat

PREVENIRE CAUZE alcoolism, vaccinare VHB, profilaxie infecie VHB, VHC (sexual, acte medicale, briciul de la frizerie, manichiur, pedichiur, stomatolog) - nu se desinfecteaz cu alcool!

DEPISTARE CAUZE SI TRATARE N STADII REVERSIBILE (hepatit, steatoz)

PERSPECTIVEAUTOTRANSPLANT DE HEPATOCITE

PROBLEMA = ARHITECTURA LOBULARA