4. - Arrêter la multiplication virale - Diminuer l’activité de l ’hépatite chronique - Arrêter l’évolution de la fibrose (régression?) - Prévenir l’évolution vers la cirrhose - Prévenir les complications - Prévenir le CHC - Prévenir la mortalité OBJECTIFS DU TRAITEMENT DE L’HÉPATITE CHRONIQUE B?
5. TEMPS AgHBe négatif ADN VHB négatif Anti-Hbe positif AgHBs négatif Anti-HBs positif OBJECTIFS DU TRAITEMENT
6. SEROCONVERSION HBs: LE CHAMPION DES CRITÈRES ADN VHB négatif Seroconversion HBe Seroconversion HBs 1 3 2
10. PHASE DE TOLÉRANCE IMMUNITAIRE = MAUVAISE RÉPONSE ADN VHB > 9 log ALAT < N AgHBe + PBH = A1F1 MULTIPLICATION VIRALE RÉPONSE IMMUNITAIRE
11. PHASE DE RÉACTION IMMUNITAIRE = BONNE RÉPONSE ADN VHB < 9 log ALAT > N AgHBe +/- PBH > A1F1 MULTIPLICATION VIRALE RÉPONSE IMMUNITAIRE
12. 10 10 2 10 3 10 4 10 5 10 6 10 7 10 8 10 9 10 10 Hépatite chronique AgHBe - Porteur inactif Martinot et al. J Hepatol 2002 CHARGE VIRALE ET STADE DE L’HC B
13. 10 10 2 10 3 10 4 10 5 10 6 10 7 10 8 10 9 10 10 1 2 3 4 Années Hépatite chronique AgHBe - Porteur inactif 5 COMMENT DISTINGUER LE PORTAGE INACTIF DE L’HCA AgHBe - LE SUIVI +++ Asselah et al. GCB 2005
14.
15. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
16. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 ADN VHB < 4 log ALAT = N
17. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - Surveiller EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 ADN VHB < 4 log ALAT = N
18. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - Surveiller EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 ADN VHB < 4 log ALAT = N ADN VHB > 4 log et/ou ALAT > N PBH > A1/F1
19. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - Surveiller EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 ADN VHB < 4 log ALAT = N ADN VHB > 4 log Et/ou ALAT > N PBH > A1F1 Traiter
32. PREDICTION DE LA RESISTANCE A L’ADV - ADN VHB < 3 log à S48 3% - ADN VHB > 3 log à S48 > 50% Marcellin et al. J Hepatol 2006
33.
34. ENTECAVIR VS LAMIVUDINE ADN VHB négatif à 1 an Chang et al. NEJM 2006 Lai et al. NEJM 2006 AgHBe - 72% 90% Lamivudine Entecavir P<0,001 AgHBe + 36% 67% P<0,001
35. ENTECAVIR DANS L’HC AgHBe + ADN VHB négatif (sous-groupe de 146/354 patients) 0 20 40 60 100 80 1 an 2 ans 3 ans 58% 85% 90% Han et al. AASLD 2007 4 ans 91% N=146 N=140 N=134 N=112 5 ans 94% N=94
36.
37.
38. TELBIVUDINE ADN VHB NÉGATIF A 1 et 2 ANS . N=1370 88% 0% 10% 20% 30% 40% 50% 60% 70% AgHBe + AgHBe - Lai et al. NEJM 2007 60%
39. TELBIVUDINE ADN VHB NÉGATIF A 1 et 2 ANS . N=1370 56% 88% 0% 10% 20% 30% 40% 50% 60% 70% AgHBe + AgHBe - Lai et al. NEJM 2007 82% 60%
54. HBs - Séroconversion HBs NÉGATIVATION ET SÉROCONVERSION HBs 3% 4% 3% 2% 0% 0% Marcellin et al. NEJM 2004
55. AgHBs NÉGATIF 1 an 2 ans 3 ans 4 ans % 5 6 9 11 0 Marcellin et al. Gastroenterology 2009 Marcellin et al. APASL 2009 12 5 ans
56. AgHBs NÉGATIF 1 an 2 ans 3 ans 4 ans % 5 6 9 11 0 Marcellin et al. Gastroenterology 2009 Marcellin et al. APASL 2009 12 5 ans 64% des patients ADN VHB -
58. HBsAg EN FONCTION DU TRAITEMENT Traitement Semaines LAM PEG-IFN -2a PEG-IFN -2a + LAM Mediane log 10 IU/mL Marcellin et al. AASLD 2009
59. HBsAg EN FONCTION DE LA RÉPONSE À 5 ANS AgHBs - AgHBs + ADN VHB ≤10 000 ADN VHB >10 000 Médiane log 10 IU/mL Semaines Traitement Marcellin et al. AASLD 2009
60. COMMENT TRAITER Guidelines EASL AgHBe + et AgHBe - EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
61. COMMENT TRAITER Guidelines EASL AgHBe + et AgHBe - EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 IFN PEG ADN VHB < 7 log ALAT > 3N
62. COMMENT TRAITER Guidelines EASL AgHBe + et AgHBe - ADN VHB à S12 EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 IFN PEG ADN VHB < 7 log ALAT > 3N
63. COMMENT TRAITER Guidelines EASL AgHBe + et AgHBe - ANALOGUE Entecavir ou Tenofovir Telbivudine si ADN<7log < 1 log à S12 EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 IFN PEG ADN VHB < 7 log ALAT > 3N
64. COMMENT TRAITER Guidelines EASL AgHBe + et AgHBe - ANALOGUE Entecavir ou Tenofovir Telbivudine si ADN<7log IFN PEG ADN VHB > 7 log ALAT > 3N
65. COMMENT TRAITER Guidelines EASL AgHBe + et AgHBe - ANALOGUE Entecavir ou Tenofovir Telbivudine si ADN<7log Si ADN + à S24-48 Changer analogue EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009 IFN PEG ADN VHB > 7 log ALAT > 3N
Therapeutic Response HBV DNA suppressed to ≤ 5 log 10 , with ALT normalized OR HBeAg loss
Therapeutic Response HBV DNA suppressed to ≤ 5 log 10 , with ALT normalized OR HBeAg loss
Therapeutic Response HBV DNA suppressed to ≤ 5 log 10 , with ALT normalized OR HBeAg loss
Long Term Evaluation-ITT Analysis: Patients who discontinued for administrative reasons with HBV DNA <400 copies/mL and no ongoing AE were excluded for visits after discontinuation (n= 7). At week 144, 9 patients were missing data at random (no evidence that they had discontinued). Of these 9 patients all had HBV DNA <400 copies/m at last available timepoint. Patients who added FTC (3) are considered failures from the time of FTDF addition (although all 3 had HBV DNA <400 copies/mL) Open Label Extension: TDF denominator: ADV denominator:
Long Term Evaluation-ITT Analysis: Patients who discontinued for administrative reasons with HBV DNA <400 copies/mL and no ongoing AE were excluded for visits after discontinuation (n= 9). At week 144, 3 patients were missing data at random (no evidence that they had discontinued). Of these 3 patients all had HBV DNA <400 copies/mL 4 patients with missing data at week 144 with HBsAg loss Patients who added FTC (31) are considered failures from the time of FTDF addition (although all 17 had HBV DNA <400 copies/mL;9>400;5DC)
Conclusion: Rates of virological response one year after EoT are similar to those 24 weeks after EoT