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 > 7 log ALAT < N AgHBe + PBH = A1F1 MULTIPLICATION VIRALE RÉPONSE IMMUNITAIRE
11. PHASE DE RÉACTION IMMUNITAIRE = BONNE RÉPONSE ADN VHB < 7 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
36. - Ultimate goal of therapy - Closest to cure - Not HBV eradication but associated with improved prognosis Marcellin et al. Annals Intern Med 1990 Loriot et al. Hepatology 1992 THE IMPORTANCE OF HBsAg LOSS
37.
38. No HBsAg loss 20 40 60 80 100 Survival (%) HBsAg loss P<0.001 309 cirrhotics with a mean follow-up of 6 years Fattovich et al. Am J Gastroenterology 1998 Time (years) 1 2 3 4 5 6 7 HBsAg Loss is Associated with Improved Survival
39. INCIDENCE DE LA NÉGATIVATION DE L’AgHBs EN FONCTION DE LA SÉROCONVERSION HBe Moucari et al. J Hepatol 2009 64% 17% p <0,001
43. HBsAg LOSS after PEG IFN ± LAM 1 an 2 ans 3 ans 4 ans % 5 6 9 11 0 Marcellin et al. NEJM 2004 Marcellin et al. Gastroenterology 2009 Marcellin et al. Hepatology International. In press 12 5 ans
44. HBsAg LOSS 1 an 2 ans 3 ans 4 ans % 5 6 9 11 0 Marcellin et al. NEJM 2004 Marcellin et al. Gastroenterology 2009 Marcellin et al. APASL 2009 12 5 ans 64% of the patients HBV DNA negative
Marcellin P et al . Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808 − 816. Lai CL et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med . 2007;357:2576−2588. Chang TT et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001−1010. Heathcote J et al. A randomized, double blind, comparison of tenofovir DF (TDF) versus adefovir diprivoxil (ADV) for the treatment of HBeAg positive chronic hepatitis B (CHB): study GS-US-174−0103. Hepatology . 2007;46(4 suppl 1):861A (Abstract LB6). Hadziyannis S et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen- negative chronic hepatitis B. N Engl J Med . 2003;348:800−807. Lai CL et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med . 2006;354:1011−1020. Marcellin P et al. A randomized, double blind, comparison of tenofovir DF (TDF) versus adefovir diprivoxil (ADV) for the treatment of HBeAg negative chronic hepatitis B (CHB): study GS-US-174-0102. Hepatology . 2007;46(4 suppl 1):290A−291A (Abstract LB2).
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
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Patients were selected for HBsAg analysis, who reached week 24 of study There were no significant differences between the 3 treatment arms