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Hépatites virales B et C et transplantation cardiaque.ppt

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Hépatites virales B et C et transplantation cardiaque.ppt

  1. 1. DU hépatites virales Janvier 2011 Pascal LEBRAY Service d’hépato-gastroentérologie Pitié-Salpêtrière
  2. 2. <ul><li>Épidémiologie des infections VHB et VHC en transplantation cardiaque </li></ul><ul><li>Évolution spontanée des hépatites B ou C, ancienne ou de novo </li></ul><ul><li>Progrès: le traitement du VHB. Avenir: traitement du VHC </li></ul><ul><li>Principes et résultats des greffes dérogatoires VHC ou VHB+ </li></ul>
  3. 4. <ul><li>Avant 1991 : Contamination fréquente </li></ul><ul><ul><li>Donneur Ag HBs + ou AcHBc + sans prophylaxie (< 1986, >10% en IdF) </li></ul></ul><ul><ul><li>Transfusion Sanguine (< 1986) </li></ul></ul><ul><ul><li>Biopsies endomyocardiques (<1991) Rosenheim M, GCB 2006 </li></ul></ul><ul><ul><li>Contamination par le chirurgien Prentice MB, BMJ 1992, Harpaz R, NEJM 1996 </li></ul></ul><ul><li>Depuis 1991: Contamination exceptionnelle </li></ul><ul><ul><li>Greffe avec donneur anti-HBc + après échec du traitement prophylaxique </li></ul></ul><ul><ul><li>Contage familial ou sexuel </li></ul></ul><ul><li>Diagnostics différentiels (rare) </li></ul><ul><ul><ul><li>Séroréversion sur infection occulte (receveur anti-HBc+/ Ag HBs-) </li></ul></ul></ul><ul><ul><ul><li>Infection chronique prégreffe </li></ul></ul></ul> >25 ans de suivi post-greffe chez les patients HBV +
  4. 5. 4 2 3 5 8 7 21 17 8 9 2 0 0 0 0 0 5 10 15 20 25 Incidence: 1984-1994 : 3,45 % [0,9-7,17%] 1995-1998 : 0 % mesures d’hygiene drastiques matériel à usage unique pour BEV 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998
  5. 6. <ul><li>Transplantation avant 1991 </li></ul><ul><ul><li>Donneur Ac HCV + (3% population médicalisée en IdF) </li></ul></ul><ul><ul><ul><li>car risque de transmission = 60-80% </li></ul></ul></ul><ul><ul><ul><li>ARN HCV détectable dans le myocarde </li></ul></ul></ul><ul><ul><li>Faguioli, JHLTransplant, 2001, Ong, Hepatology 1999 </li></ul></ul><ul><ul><li>Transfusion Sanguine </li></ul></ul><ul><ul><ul><li>Car risque de transmission = 80% </li></ul></ul></ul><ul><li>Transplantation depuis 1991 </li></ul><ul><ul><li>261 (2%) greffes aux USA entre 1994 et 2003 si UNOS 1 ou greffe marginale </li></ul></ul><ul><ul><li>non utilisation en France mais possible si receveur VHC négatif </li></ul></ul><ul><ul><li>Transmission via personnel soignant (Chirurgien) Esteban, NEJM 1996 </li></ul></ul><ul><ul><li> </li></ul></ul> > 20 ans de suivi post-greffe chez les patients HCV +
  6. 7. Auteur Cadranel (GHPS) Drescher Wedemeyer Lunel (GHPS) Grossi Année 1991 1994 1998 2000 2001 Etude rétrospective rétrospective rétrospective prospective rétrospective N 80 243 436 874 781 % AgHBs+ 16 27 17 9 2,5 < 3 % des transplantés cardiaques sont Ag HBs+
  7. 8. Auteur Cadranel Lunel Lunel Année 1991 1995 2000 Etude rétrospective rétrospective rétrospective N 80 469 874 Ac VHC+ (%) 20 PCR + (%) Pré TC Ac ou PCR+ (%) 0 4 1 Post TC 10,4 7 5 % des transplantés cardiaques sont PCR HCV+
  8. 10. Greffe Infection de novo <ul><li>Hépatopathie préexistante du receveur </li></ul><ul><ul><li>Infection chronique B ou C </li></ul></ul><ul><ul><li>(< 2%) </li></ul></ul><ul><ul><li>Foie cardiaque /OH /NASH (+++) </li></ul></ul>Greffon positif (3%) Ac Hbc+/ PCR VHC+ Contage périopératoire Contage tardif Immunosuppression Facteurs influençant l’évolution spontanée des hépatites B et C Protection anti-VHB du receveur Vacciné / guéri / naïf / sous prophylaxie
  9. 11. <ul><li>Etiologies d’une cytolyse > 5 N ou cholestase aigue après greffe cardiaque: </li></ul><ul><ul><ul><li>Dysfonction myocardique, </li></ul></ul></ul><ul><ul><ul><li>Sepsis </li></ul></ul></ul><ul><ul><ul><li>Hépatite médicamenteuse (bactrim, IS, hypolipémiants) </li></ul></ul></ul><ul><ul><ul><li>CMV…EBV, HSV …. </li></ul></ul></ul><ul><ul><ul><li>Lithiase de la VBP (si Néoral++) </li></ul></ul></ul><ul><ul><ul><li>Réactivation HBV </li></ul></ul></ul><ul><ul><ul><li>Fibrose Hépatique Cholestasiante B ou C (sur infection préexistante ou de novo) </li></ul></ul></ul><ul><ul><ul><li>IgM HAV, HEV aigue ou chronique </li></ul></ul></ul><ul><ul><li>Diag HBV(+) si Ag HBs + / PCR HBV> 4log / pas d’autre diagnostic </li></ul></ul><ul><ul><li>Diag HCV(+) : PCR HCV+ > 4 log / pas d’autre diagnostic </li></ul></ul>
  10. 12. <ul><li>Hépatite chronique ou de novo </li></ul><ul><li>Début avant M3 </li></ul><ul><li>Évolution subfulminante </li></ul><ul><li>Cholestase biologique et histologique (prolifération ductulaire, péricholangite) mimant une obstruction biliaire </li></ul><ul><li>Fibrose portale extensive </li></ul><ul><li>Virémie élevée VHC ou VHB > 7 log 10 UI /ml </li></ul><ul><li>PCR in situ : 80% des hépatocytes + </li></ul>Lim et al. Gastroenterology 1994
  11. 13. <ul><li>Cas clinique 1 : Seroreversion B </li></ul><ul><ul><ul><li>>10 ans post-greffe : profil de guérison du receveur </li></ul></ul></ul><ul><ul><ul><li>01/07 : bolus CORTICOIDES pour rejet sévère </li></ul></ul></ul><ul><ul><ul><li>07/07 : Ac HBs+  Ag HBs+, PCR HBV > 10 5 log UI/ml, ALT> 5n </li></ul></ul></ul><ul><ul><ul><li>11/07 : sous baraclude: ALT nles et PCR < 3 log, PBH : A1F1 </li></ul></ul></ul><ul><ul><ul><li> Séroréversion possible si IS majorée </li></ul></ul></ul><ul><ul><li>Cas clinique 2: Sérologie Ac VHC 2 ème ou 3 ème génération faussement négative </li></ul></ul><ul><ul><ul><li>patient greffé depuis 15 ans, </li></ul></ul></ul><ul><ul><ul><li>hépatopathie chronique post greffe (F3-F4) étiquetée NASH </li></ul></ul></ul><ul><ul><ul><li>IRC pré dialyse </li></ul></ul></ul><ul><ul><ul><li>Sérologies HCV toujours négatives </li></ul></ul></ul><ul><ul><ul><li>PCR + sur analyse rétrospective du sérum </li></ul></ul></ul><ul><ul><ul><li> Faire ARN VHC (> Ac VHC ) si ↑ ALAT et facteurs de risque </li></ul></ul></ul>
  12. 14. <ul><li>60% Infection virale B ou C chronique active +++ </li></ul><ul><ul><li>Peu d’évolution sévère à 2 ans mais CIRRHOSE RAPIDE </li></ul></ul><ul><li>35% Portage asymptomatique </li></ul><ul><li>Malgré une c harge virale souvent très élevée </li></ul><ul><li>5% Hépatopathie aigue, subaigue </li></ul><ul><ul><li>Hépatite fibrosante cholestatique Zylberberg, Transplantation 1997 </li></ul></ul><ul><ul><li>Lau, Gastroenterology 1992 </li></ul></ul><ul><ul><li>Réactivation virale B </li></ul></ul><ul><ul><li>Décès rapide </li></ul></ul>
  13. 15. Auteur Cadranel Zein Smith Fagiuoli Ong Année 1991 1995 1995 1997 1999 n 20/80 4/59 6/? 12/155 23/485 Evolution 1 cirrhose (M14) 1 FHC 2 IHC* (M45,M87) 2 IHC* (M50,M56) 4 FCH (3 décès ) * insuffisance hépatocellulaire
  14. 16. Grossi 2001 Lunel 2000 Wedemeyer 1998 Nb 11 (de novo/ R+) 69 (95%de novo) 74 (93% de novo) Apparition Ag HBs 21 mois (5-130) 22 mois 25 mois % hépatite chronique 45% sévère 84% à 1 an (ALT) 100 % HBV-DNA >5 log 10 9+ / 11 CV élevée Histologie/ Décès 3 décès 3 (sub)fulm 2 cirrhoses 3 décès (37% des décès) F3-F4 : 56% 17% de décès Suivi (ans) 8.5 9
  15. 17. <ul><li>OPTN/UNOS 2000-2005 </li></ul><ul><li>Survie à 1,3 et 5 ans: </li></ul><ul><ul><li>Rec. HCV+ (n= 224): 85%, 77%, 69% </li></ul></ul><ul><ul><li> vs. vs. vs. </li></ul></ul><ul><ul><li>Rec. HCV- (n> 10.000): 88%, 81%, 74% </li></ul></ul><ul><ul><li>Risque ajusté : NS </li></ul></ul><ul><ul><li>rejet sévère ? Coronaropathie du greffon ? </li></ul></ul>Fong TL, Transplantation 2009  Evolution hépatique à court terme satisfaisante
  16. 18. <ul><li>Padoue, 85-96, 360 patients transplantés(R), 49 infectés: </li></ul><ul><li>47% infection prégreffe, 53% infection de novo </li></ul><ul><li>absence de signe clinico-bio-morphologique d’hépatopathie en prégreffe. </li></ul><ul><li>Cortico-cyclo-aza </li></ul><ul><li>suivi 5 ans (HBV) et 8 ans (HCV) </li></ul>8 (7)* cirrhoses, 4 (3)* décès liés à la maladie hépatique *( ) = de novo Rec. ou Don. HCV ou HBV+: Evolution hépatique à moyen terme péjorative
  17. 19. <ul><li>cardiaque </li></ul><ul><ul><li>Cas clinique 3: Fibroscan ® et Insuffisance cardiaque </li></ul></ul><ul><ul><ul><li>Patient transplanté cardiaque (1987) </li></ul></ul></ul><ul><ul><ul><li>HCV+ de novo non traité </li></ul></ul></ul><ul><ul><ul><li>A1F1 (1999) </li></ul></ul></ul><ul><ul><ul><li>Bilan pré Retransplantation cardiaque: Suspicion de cirrhose (2007) </li></ul></ul></ul><ul><ul><ul><li> L’insuffisance cardiaque droite surestime le Fibroscan </li></ul></ul></ul>Lebray P, Hepatology 2009  Le fibrotest étant fréquemment non interprétable (40% des cas), la PBH reste un « gold standard  » imparfait Pré greffe Post greffe M + 6 ALT nl nl 64 UI/l Fibroscan 44,3 kPa 3,8 kPa 6,4 kPa Fibrotest A1F1 PBH Congestion A1F1
  18. 21. Lunel , Gastroenterology 2000 patients contrôles plus sévères ! = biais de sélection ? P = N.S ?
  19. 22. Wedemeyer JVHepatitis 2006+ Gastroenterology 2001 +Transplantation 1998 <ul><li>HBV DNA élevée (85% des cas) </li></ul><ul><li>56% de fibrose extensive ou cirrhose (F3-4) à 8 ans </li></ul><ul><li>2 CHC </li></ul><ul><li>Décès liés au foie : 17% à 8 ans, 27% à 11 ans </li></ul><ul><li>(vs. 0% si traitement antiviral efficace) </li></ul>p < 0.05
  20. 23. Registre US des transplantés cardiaques (1994-2003) Suivi médian de 4 ans Régression logistique + pondération selon les facteurs confondants Ajustement selon l’âge du receveur et le statut VHC du receveur <ul><li>Mortalité (Donneur Ac HCV+ vs HCV -) </li></ul><ul><li>à 1 an: 16.9% vs 8.2% </li></ul><ul><li>à 5 years : 41.8% vs 18.5% </li></ul><ul><li>à 10 years : 50.6% vs 24.3% ( P< .001). </li></ul><ul><li>↑ décès hépatique: 13.7% vs 0.4% </li></ul><ul><li>↑ décès par coronaropathie: 8.8% vs 4% </li></ul><ul><li>↓ rejet cardiaque: 7.8% vs 16.5% </li></ul>Gasink LB: JAMA 2006
  21. 25. <ul><li>Potentiellement utile si fibrose évolué (> F2) car IMPOSSIBLE en post greffe et évolution péjorative (QS) </li></ul><ul><li>Indication limité par le risque inhérent au traitement en phase d’insuffisance cardiaque terminale: </li></ul><ul><ul><li>Interferon pegylé : Cardiomyopathie (Troubles du rythme) </li></ul></ul><ul><ul><li>Ribavirine : anémie et complication ischémique ou Insuffisance cardiaque par hyperdébit compensateur </li></ul></ul><ul><li>A discuter si traitement court (Génotype 2-3-4, CV faible, IL28B), absence de cardiopathie ischémique ou dysrythmique non appareillée, hors décompensation cardiaque et sous surveillance hépatologique et cardiologique rapprochée (+++) </li></ul><ul><ul><li>Ex . Local : </li></ul></ul><ul><ul><ul><li>Patient 1: Cardiopathie congénitale + ex-IVDU, ascite, génotype 2 et F2, PEG-Riba efficace per TTT, ILA, décès </li></ul></ul></ul><ul><ul><ul><li>Patient 2: Cardiopathie droite dysrythmique avec défibrilateur, ascite , OH + ex-IVDU, génotype 2, F4, PEG-Riba efficace x 9 mois, PCR nég depuis M1  EOT, en attente de double greffe cœur-foie </li></ul></ul></ul>
  22. 26. <ul><li>INTERFERON contre indiqué </li></ul><ul><li>Wang BY, Ann Thorac Surg 2010 </li></ul><ul><li>Ribavirine et monothérapie: pas d’étude </li></ul><ul><li>Acide ursodesoxycholique ? </li></ul><ul><li>AVENIR </li></ul><ul><ul><li>…… multithérapies par antiprotéase ou antipolymérase </li></ul></ul><ul><ul><li>…… Interféron Pegylé + Riba à distance de la greffe ??? </li></ul></ul>
  23. 27. <ul><li>Étude pilote, ALFERON ® ( Interféron leucocytaire naturel ): </li></ul><ul><li>n = 2 HBV + 4 HCV + 1 HBV-HCV ( tous génotype 1ou anti-HBe+) </li></ul><ul><li>8,5 ans post TC [7-16] </li></ul><ul><li>6 MU x 3/sem x 1 an et FU: +1 an </li></ul><ul><li>Groupe traité (7) vs. non traités (9) vs. non infectés (14) </li></ul><ul><li>Rejet : </li></ul><ul><ul><ul><li>1/7 rejet grade 3 (ISHLT) (favorisé par un arrêt de la cyclosporine) </li></ul></ul></ul><ul><ul><ul><li>Pas d’augmentation du taux de rejet vs. contrôles </li></ul></ul></ul><ul><li>Réponse : </li></ul><ul><ul><ul><li>Répondeurs biologiques : 7/7 </li></ul></ul></ul><ul><ul><ul><li>ALT normales persistantes à 1 an : 6/7 </li></ul></ul></ul><ul><ul><ul><li>Répondeurs virologiques : 6/7 </li></ul></ul></ul><ul><ul><ul><li>PCR négative à 1 an post FU : 3/7 !! </li></ul></ul></ul>Fagiuoli, Transplantation 2003 Immunostimulation de l’IFN limité par un phénomène de tolérance tardive ?
  24. 28. <ul><li>9 patients Ag HBs+ inactifs pré greffe </li></ul><ul><li>ALT nles, ADN HBV < 200.000 cop/ml </li></ul><ul><li>Réactivation post greffe: 7/9 </li></ul><ul><li>Contrôle par Lamivudine : 7/7 </li></ul><ul><li>Réactivation (Lam-R) à 2 ans : 3/7 </li></ul><ul><li>Contrôle par Adéfovir : 3/3 </li></ul>Zampino R, Transplantation 2005 <ul><li>Poursuite d’un traitement efficace </li></ul><ul><li>Options: Traitement prophylactique ou si réactivation virale </li></ul><ul><li>Surveillance PCR / transa / 3 mois </li></ul>
  25. 29. <ul><li>Lamivudine la plus étudiée +++ (Zeffix , Epivir 100 mg/j p.o) </li></ul><ul><ul><li>Hépatite aiguë sévère ou chronique active </li></ul></ul><ul><ul><li>Efficace et bien tolérée </li></ul></ul><ul><ul><ul><li>Diminution de la charge virale, normalisation ALT, séroconversion Ag  Ac anti-HBe et amélioration histologique. </li></ul></ul></ul><ul><ul><li>Résistance fréquente à moyen terme </li></ul></ul><ul><ul><ul><li>63% après 14 mois </li></ul></ul></ul><ul><ul><li>Limite le risque de cirrhose ou de CHC (?) </li></ul></ul><ul><li>Avenir : Analogues nucleo(s)(t)idiques adaptés à la Cl. Créat+++ </li></ul><ul><ul><ul><li>Entécavir (Baraclude) (1 cp/j ) </li></ul></ul></ul><ul><ul><ul><li>Ténofovir (Viread) (1 cp/j) > Adéfovir (Hepsera) </li></ul></ul></ul><ul><li>Interferon contre indiqué !! (rejet+++) </li></ul><ul><ul><li>Dulai, Transplantation 1999, </li></ul></ul><ul><ul><li>Grossi, Transplant Proc 2001, </li></ul></ul><ul><ul><li>Ko, J Heart Lung Transpl 2001 </li></ul></ul>
  26. 30. <ul><li>20 patients Ag HBs+ , FU 8 ans (1996-2004) </li></ul><ul><li>19/20 de novo, 90% Ag HBe+ </li></ul><ul><li>F0-1 (20%), F2-3 (20%), F4 (60%) </li></ul><ul><li>5% HBV inactif non traité </li></ul><ul><li>Famciclovir : RV 1 (6%) , Résistance 16 </li></ul><ul><li> Lamivudine : RV 5 (33%), résistance 10 </li></ul><ul><li> Adéfovir : RV 3 ou Ténofovir : RV 1 </li></ul><ul><li>Séroconversion HBe (45%) mais jamais HBs (0%) </li></ul><ul><li>Régression de fibrose 6/7 , de cirrhose 2/3 </li></ul><ul><li>5% CHC </li></ul><ul><li>Chez patients avec Résistance virale : 100% des décès liés au foie </li></ul>Potthoff A, J Viral Hep 2006 Indications identiques aux sujets non greffés (HBV répliquante et active) Monothérapie efficace Si CV élevée, risque de résistance des analogues de 1 ère génération  ETV et/ou TNF d’embléé ? Intêret du traitement prophylactique non démontré
  27. 31. <ul><li>Carence de protection </li></ul><ul><ul><li>6% des patients transplantés sont vaccinés </li></ul></ul><ul><ul><li>65% absence de protection </li></ul></ul><ul><ul><li>26% guéris Grossi, 2001 </li></ul></ul><ul><li>Déficit de réponse humorale </li></ul><ul><ul><li>40% de séroconversion post vaccinale </li></ul></ul><ul><ul><li>20% si NYHA 4 </li></ul></ul><ul><ul><li>50% si 2 séries vaccinales Foster, ISHLT 2005 </li></ul></ul><ul><li>Risque mineur si vacciné ? </li></ul><ul><ul><li>23 Receveurs Ac HBs + </li></ul></ul><ul><ul><li>Pas de prophylaxie antivirale </li></ul></ul><ul><ul><li>A ucune séroréversion Ag HBs + Wang, Transplantation Proceedings 2004 </li></ul></ul>Dépister et vacciner précocement si indication TC
  28. 33. <ul><li>Objectifs </li></ul><ul><ul><li>augmenter le pool de greffons </li></ul></ul><ul><ul><li>Limiter la mortalité sur liste </li></ul></ul><ul><ul><li>Ne pas augmenter la morbi-mortalité en post greffe </li></ul></ul><ul><li>pool de donneurs en Ile de France: </li></ul><ul><ul><li>Ac HBc + : 13% </li></ul></ul><ul><ul><li>Ac VHC+ : 1 à 5% </li></ul></ul>
  29. 34. <ul><li>Si urgence vitale : Donneur Ag HBs+ </li></ul><ul><li>« Si absence d’alternative et pronostic vital engagé » : </li></ul><ul><ul><li>Donneur Ac HBc+ /Ag HBs- (AcHBs +/-) quelque soit le statut VHB du receveur </li></ul></ul><ul><ul><li>Donneur Ac HCV+ si et seulement si receveur PCR HCV positif </li></ul></ul><ul><ul><li>Consentement écrit du patient en attente </li></ul></ul>
  30. 35. De Feo, Transplantation Proceedings 2005 <ul><li>Absence de dépistage de l’anti-HBc en Italie avant 2002 </li></ul><ul><li>Analyse rétrospective du sérum des receveurs </li></ul><ul><li>Greffon AgHBs- / Ac HBc+ </li></ul><ul><li>Pas de prophylaxie </li></ul>
  31. 36. <ul><li>Donneurs : </li></ul><ul><ul><li>274 Donneurs anti-HBc+ et 6 Donneurs Ac VHC+ (sur 69 proposés) </li></ul></ul><ul><li>Receveurs : </li></ul><ul><ul><li>5% de greffes supplémentaires ! </li></ul></ul><ul><ul><li>572 greffes anti-HBc+ dont TR (412), TH (125), TC(21) , TP (13), Visage (1) </li></ul></ul><ul><ul><ul><li>aucun cas authentifié de transmission du VHB chez le receveur vacciné </li></ul></ul></ul><ul><ul><ul><li>4 receveurs hépatiques et non vaccinés contaminés </li></ul></ul></ul><ul><ul><ul><li>8% séroconversion anti-HBc </li></ul></ul></ul><ul><ul><li>12 greffes anti-VHC+ dont TH (6),TR (5), TC (1) </li></ul></ul><ul><ul><ul><li>40% de Donneur PCR + </li></ul></ul></ul><ul><ul><ul><ul><li>+/- changement de génotype chez le receveur </li></ul></ul></ul></ul><ul><li>Sous-utilisation en TC : </li></ul><ul><ul><li>7.5% des greffons cardiaques dérogatoires proposés sont utilisés </li></ul></ul><ul><ul><li><2% des greffes cardiaques sont des greffes dérogatoires </li></ul></ul>
  32. 37. Donneur: sérologie VHC+ Protocoles dérogatoires (AFSSAPS)
  33. 38. Donneur HBc+
  34. 39. <ul><ul><li>Rôle de l’hépatologue en Transplantation cardiaque </li></ul></ul><ul><ul><ul><li>Anciens patients greffés et infectés </li></ul></ul></ul><ul><ul><ul><ul><li> traitement du VHB, encore attendre pour le VHC </li></ul></ul></ul></ul><ul><ul><ul><ul><li> dépistage de la cirrhose et du CHC </li></ul></ul></ul></ul><ul><ul><ul><li>Receveurs HBV ou HCV </li></ul></ul></ul><ul><ul><ul><ul><li> Pas de contre indication à la greffe en l’absence de fibrose sévère </li></ul></ul></ul></ul><ul><ul><ul><ul><li> traitement HBV classique, discuter le traitement anti-HCV sous contrôle </li></ul></ul></ul></ul><ul><ul><ul><ul><li> évaluation histologique+++ </li></ul></ul></ul></ul><ul><ul><ul><ul><li> discuter greffe combinée cœur/foie si F3-4 </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>UNOS TH+TC (n = 47): 6 VHC+ </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>GHPS TH+TC (n = 9) dont 1 patient VHB+ (3 ans), 1 VHC guéri /CHC+ (DC précoce / sepsis mycotique), 1 VHC+ EOT PCR nég en attente. </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Greffes dérogatoires depuis 2006 </li></ul></ul></ul><ul><ul><ul><ul><li> vaccination anti-VHB systématique en prégreffe </li></ul></ul></ul></ul><ul><ul><ul><ul><li> IgHBs +/- Lam à vie car réactivation virale potentielle </li></ul></ul></ul></ul>AU TOTAL : Prise en charge spécialisée et multidisciplinaire ++++

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