Forme speciale de ciroz hepatic

A. CH postviral cea ma frecvent Morfologie : macronodular debut portal al fibrozei S.M. mai mare ca n CH Alc. markeri virali + Tratament : Entecavir/Tenof/Lami (CH VHB+) x 12 luni PegIFN+Riba (CH VHC+) x 24s x Vaccinare anti-A si anti-B (CH VHC+) B. Ficatul alcoolic : Totalitatea leziunilor morfopatologice asociate cu un spectru larg de manifestri clinicopatologice induse de consumul de alcool Etiologia : consum cronic (10% americani) 1/3 fr afectare hepatic 70% = ficat gras /H alc. /CH (8% - 20%) Factori de risc : 20 - 40g/zi B; 10 20g/zi - F 30g/zi x 10 ani CH = > 600 Kg B > 150 300 Kg F a) sexul feminin, varsta, excesul ponderal, factori genetici /nutriionali(malnutritia), asocierea VHC Morfologie : a) Ficatul gras alcoolic : steatoz hepatic macrovezicule lipidice ( lipogranuloame rar) proliferare REN megamitocondrii b) Hepatit alcoolic : nu obligator preciroz (transjugulara) o degenerare balonizant hepatocite, steatoz macroveziular, colestaza i.hepatic o mitocondrii gigante o II cu PMN preponderent o hialin alcoholic necroze: hialin, scleroas acut o fibroz periportala/intrasinusoidal/perivenular c) C.H. alcoolic : micronodular

Ficatul gras alcoolic HM asimptomatic 2/3 Eco) Dupuytren, atrofie testicular, eritem palmar Chwostek, ginecomastie rar : astenie fizic, dispepsie, HM dureroas, colestaz S. Zieve : hiperlipemie/an. hemolitic/dureri abdomen Laborator : BT ( 25 % ) AST/ALT 2 GGT, FAS GGT/FAS > 5 Dgs+ : PBH Eco : hiperecogenicitate difuz / atenuare posterioar 2. Hepatita alcoolic : a. asimptomatic PBH b. simptomatologie comun : anorexie, grea, astenie fizic, icter, T0, malnutriie c. complicaii : EH, HDS, ascit (hepatit acut) H.M (95 %) dureroas ; - S.M. semne de afectare hepatic cr. + alcoolism, T0 ( H. subacut) Laborator : anemie, leucocitoz (> 40.000/mmc) cu PMN AST, ALT (AST/ALT > 2), GGT, FAS, BT albuminemie, colesterol, INR transferina carbohidrat deficient, etil glicuronidul VEM Tratament : sistare alcool, corectare deficiene nutriionale(vit.,ac.folic,B1, K+, fitomenadion) pentoxifilin 400mg p.o. x 3/zi x 4s corticoterapie: P=40mg/zi x >4-6s (forma transplant hepatic: supravieuire + I.Hep. dup Hep.Alc., abstinen >6 l 3. C.H. Alcoolic Clinica : 10% - 20% asimptomatic aspect comun al CH pregnant manifestri hipogonadism/feminizare

Clinica

benzi fibroase sp. P V. C L steatoz + lez. hepatit hialin alcoolic cantitate Fe ++

semne impregnare alcoolic : Dupuytren, hipertrofie parotide polineuropatie senzitivo-motorie m. inf. rinofima, pancreatit cr., CMD VE apar precoce/S.M mai v. CH viral

Laborator : moderat AST/ALT, GGT albuminemie, gamaglobuline (4g%) IgG, IgA, TQ VEM, ac. Uric

Tratament : x vaccinare anti-A si anti-B diet, suplimentare vit. B, E, silimarin, betain antifibrozant : polienilfosfatidilcolin UDCA 10-15mg/Kc/zi tratamentul complicaiilor CH transplant hepatic ortotop : abstinen Alc >6 luni absena af. extrahepatice stabilitate socioeconomic Ch P = C C. Ciroza biliar primitiv etiologie necunoscut patogenez autoimun distrucia ci biliare intrahepatice AAM+ colestaz Morfologic st. I : II (L, Pl, E, His) priductular st. II : II penetrant i n lobulii hepatici (piecemeal necrosis) proliferarea ductelor biliare portale septuri fibroase penetrante n lobuli st. III : disecie lobulilor de ctre septurile fibroase,scade II st. IV : C.H., absena biliductelor n port C% de Cu++ hepatic Patogeneza : autoimun : auto Ac anti-ducte biliare LTcCD8+

HLA II (DR 2, 3, 4, DP, DQ) Ac anti-mitocondriali M2+ asocierea cu alte boli auto-imune : Ty, CREST, PR, S. Sjgren

Clinica : 90% - F/40 60ani prurit, astenie = preced cu 6-12 luni icter colestatic tegument ngroat, leziuni grataj, uscat/xantoame H.M., S.M. complicaii CH = tardiv HTp (VE, As) malnutriie : osteoporoz (fracturi) deficit A, D, E, K complicaii : colangiocarcinom neo sn

Laborator : AAM M2 > 1/40 (100%) IgM (90%) hipercolesterolemie, FAS >2xN, GGT >5xN BT, lipemia ALT, AST = 1-5 x N - FR + (70%), ASMA, ATy ECO = absena diltrii ci biliare intrahepatice ERCP = CBP normal/LB frecvent PBH+: leziuni floride ale biliductelor

Tratament : transplant hepatic n stadiul terminal pretransplant, simptomatice UDCA 10-15mg/Kc/zi MTX 15mg/zi/colchicin Aza/ciclosporin A P = icter, perioada scurte colestiramin (prurit) 4g x 3/zi, naloxona, gabapentin, rifaximin plasmaferez corectarea malabsorbiei/deficite vitaminice/osteoporoza CBP+boala autoimuna: CST + UDCA

DD : Colangita sclerozant primitiv BII 70% B cu CU (rar BC) fibroz retroperitoneal/mediastinal etiologie necunoscut : genetic (HLA II, boli autoimune) anomalii imunologice Morfologie : fibroz concentric pericanalicular (stenoze/dilataii) afectare c.b. extrahepatice Clinica : frecvent asimptomatic colestaz cronc peste 3 luni (icter, prurit, HM)

Laborator : FAS, absena AAM ANCA + PBH+ ERCP + : aspect de mtnii ale c.b. intra/extrahepatice Tratament : transplant hepatic UDCA + MTX (iniial) drenaj biliar/dilatare c.b. stent

D. Ciroza cardiac : Patogenez : staz retrograd venoas dilatare V hepatice + centrolobular hipoxie necroze hepatocite fibroz centrolobular stelat CH Cauze : Sm , pericardita constrictiv, CPC > 10a, cardiomiopatie Clinica : af. cardiac cronic absena SM, As cu P > 2,5mg%, hemoragic Laborator : albuminemie, TQ, ALT, AST uor

E. Hemocromatoza ereditar Fe: absorbie crescut depunere: ficat, pancreas, cord, articulaii, gl.pituitar . Frecvena: 1/10 heterozigot 1/200 homozigot 20 40 ani

Clinica: - astenie, inapeten - cardiomiopatie, tulburari de conducere, I.cardiac - ciroza hepatica, CHC - artropatie distructiva MCF II si III - hipogonadism hipogonadotropic - disfuncie tiroidian - DZ tip II - hiperpigmentare cutanat - porfirie cutanat tarda

Hemocromatoza ereditar: diagnostic Saturaia transferinei >50%(F), >60%(B) Feritina crescut: > 250g/L PBH: hemosiderin n hepatocitele periportale indexul Fe hepatic >1,9 moli/g Genotipare Tratament: flebotomii repetate Risc: carcinom hepatocelular Steatohepatita nonalcoolic ncrcare gras hepatic n absena consumului de alcool (20g/zi) = Ficat Gras NonAlcoolic a) Microvezicular : asociere frecvent cu disfuncie H b. congrenitale, sarcin, S. Reye b) Macrovezicular : obezitate, alcool, DZ, b. metabolice congenitale, VHC 3 asociere cu necroinflamaie ihepatic Etiologie SHNA a) obezitate centrala/scadere rapida in G b) alimentaie parenteral total c) sindrom metabolic: rezistenei la insulin d) VHC-3,medicemente:CST,amiodarona,estrogeni e) B.endocrine:ov.polikistic,hipoTy,-pituitarism

Patogeneza : a) incarcare grasa hepatica b) stres oxidativ generat de RLO - endotoxemie - citokine proinflamatorii

= inflamaie fibroz Morfologie : - Tip I = ficat gras nonalcoolic - Tip II = ficat gras + inflamaie difuz (SH) - Tip III = ficat gras + hepatocite balonizate,anomalii mitocondriale - Tip IV = ficat gras + balonizare + fibroza perisinusoidala +/- inflamaie lobuli Clinica : F (65% - 80%), NAFLD=20-30%,NASH=2%-3% frecvent asimptomatici; lipohipertrofie dorsocervicala hepatalgii, astenie fizica H.M. 30% n stadiul de CH Index Ficat Gras: BMI, circumferinta abdomen, GGT,TGL Laborator : 2/3 TFH = N ALT,AST x2-3N; ALT>AST FAS, GGT = 2-3 x N (hipoalbuminemie, crestere BT) +/- feritina (>50% din pacienti) Eco :hiperecogen difuz, ficat>rinichi, estompare vase Spectroscopia RMI, Fibromax PBH = digs. Cert

Evoluia : Tratament :

benign prin eliminare f. etiologici CH : 21% - 28% eliminare f. risc UDCA 10-15mg/Kc/zi x 6-12 luni betain 20g/zi, N-acetilcistein 1g x 3/zi, vit. E 4-6 l Rosiglitazona, pioglitazona, metformin

Carcinomul hepatocelular CH : CHC : - 85% din NH primitiv - la F (2/1), loc 5/3 deces Neo - 70% Asia, Africa w

hepatocelular fibrolamelar Hepatoblastom

Biliar : colangiocarcinom chistadenocarcinom

Mezenchim : angiosarcom leiomiosarcom rabdomiosarcom Etiologia : a) VHB : b) VHC :

Asia, Africa endemic, perinatal (tineri) proliferarea hepatocitelor integrare n genomul gazdei interaciune proteine VHB gazd risc 100 x 17,5 x risc domin n rile dezvoltate alcoolul efectul carcinogen

c) Alcoolul : efecte mutagene (40g/zi 20g/zi) d) CH = 3% fac CHC e) Aflatoxina B1 = Aspergillus flavus,hemocromatoza idiopatic, porfiria, contraceptive orale - sindrom metabolic/SHNA Morfologie : nodular/masiv noduli satelii/difuz + CH/N Dgs+ : Tumori mari : clinic + imagistic a) B.H. cronic tumor hipervascularizat la TC/RMI b) alfa FP 400ng/ml c) Eco PBH : citologie prin aspiraie nodul hiper/hipo ecogen Criterii diagnostic Criterii neinvazive : pentru cei cu CH 1. Rx: 2 imagini TC/RMI n care s coincid leziuni focale peste 2 cm cu hipervascularizare arterial 2. Criterii combinate : 1 imagine Rx + alfa FP leziuni peste 2 cm cu hipervascularizaie arterial alfa FP 400ng/ml Supraveghere : ECO, alfa FP la cei cu VHC/VHB, CH x 2/an lent 1 lun clinic asimptomatic iniial hepatalgii, icter

Tratament : a) CHC pe ficat normal = rezecie hepatic (dimensiuni/nr tumori) b) CHC pe CH = transplant/segmentectomie c) CHC inoperabil : inj.i.t/termoablaie/chimioterapie - sorafenib/Rx terapie paliativa

Colangiocarcinomul Tumor malign epitelial a arborelui biliar 10% - 15% din neo hepatobiliar (II dup CHC) B>F, > 70 ani Factori patogeni: inflamaia cr ac. Biliari Factori de risc: - anomalii congenitale biliare - CSP = 42% au Ch.C. - parazitoze cu tropism biliar - litiaz biliar intrahepatic (5% Asia) - purttorii cronici - infecie tifoid - dioxin, clorur de vinil, torotrast - hepatitele cr. virale, CH, alcool, obezitatea, DZ, ficatul gras Localizare: C.B. extrahepatice: perihilar ( 50% - 60%) extrahepatic distal (20%) Ch. C. intrahepatic: tum. Localizat (20%) . Tip I = sub confluna canalelor dr i stg . Tip II = prinde confluena dar nu i canalele . Tip III = CBP + canalul dr sau stg . Tip IV = multicentric / confluena i cele 2 canale / implicare segmentar intrahepatic bilaterala

A. Ch.C. extrahepatic Diagnostic: a. Clinic: - icter colestatic (perihilar,extrahepaic) - colangit (CBP) - alterarea strii generale - decelare ntmpltoare

a. Laborator: - FAS, G-GT, BT (D), INR - albuminemie, Hb, ALT/AST ( obstructie ac./colangita) - Ca 19 9 > 100 U/ml - vit. liposolubile (A, D, E, K) B. Ch. C. Intrahepatic a) Clinic: - dureri abdominale, G, alterare stare general, apetit, tumora palpabil +/b) Laborator: - uoar FAS, CA 19-9 c) Imagistic (A/B): - ecografie (confuzie meta) - TC spiral cu ntrire de contrast - colangio TC/ colangio- RMN - angiografie TC/RM - Eco-endoscopie + ghidare aspiraie pe ac fin - PET = metastaze - ERCP + citologie de brasaj (colangioscopie) Diagnostic diferenial carcinom de V.B. sindrom Mirizzi stenoz focal benign de CBP (postop., colangiopatie ischemic, vasculite, HIV, TBC, radioterapie, disfuncie Oddi etc.) Tratament Chirugical: Ch.C. intrahepatic (40% - 60% s.v/3a) hilar, fr meta Transplant hepatic Terapie paliativ: formele nerezecabile: stent, drenaj biliar percutan, radioterapie, terapie fotodinamic, necroz cu US endoscopic, chemoembolizare, chemoterapie