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TRAITEMENT
DE L’HÉPATITE B
Patrick Marcellin
L’HÉPATITE B EN FRANCE
- 0,7% (300.000) porteurs chroniques*
- 3ème cause de cirrhose et CHC
- Mortalité: 1500/an**
- < 15...
POURQUOI TRAITER?
OBJECTIFS DU TRAITEMENT DE
L’HÉPATITE CHRONIQUE B?
- Arrêter la multiplication virale
- Diminuer l’activité de l ’hépatite...
OBJECTIFS DU TRAITEMENT

AgHBe
ADN VHB négatif
négatif

Anti-Hbe
Anti-HBs
positif AgHBs positif
négatif

TEMPS
SEROCONVERSION HBs:
LE CHAMPION DES CRITÈRES
Seroconversion
HBs

ADN VHB
négatif

3

Seroconversion
HBe

1

2
QUI TRAITER
COMMENT OPTIMISER LE TRAITEMENT DE
L’HÉPATITE CHRONIQUE B?

-Traiter les malades qui en ont besoin
(risque de complication...
HEPATITE CHRONIQUE B =
MULTIPLICATION VIRALE/RÉPONSE
IMMUNITAIRE

MULTIPLICATION
VIRALE

RÉPONSE
IMMUNITAIRE
PHASE DE TOLÉRANCE IMMUNITAIRE
= MAUVAISE RÉPONSE
ADN VHB > 7 log
AgHBe +
MULTIPLICATION
VIRALE

ALAT < N
PBH = A1F1
RÉPON...
PHASE DE RÉACTION IMMUNITAIRE
= BONNE RÉPONSE
ADN VHB < 7 log
AgHBe +/MULTIPLICATION
VIRALE

ALAT > N
PBH > A1F1

RÉPONSE
...
CHARGE VIRALE ET STADE DE L’HC B
10 10
10 9
10 8
10 7
10 6
10 5
10 4
10 3
10 2
10

Hé patite
chronique
AgHBe Porteur
inact...
COMMENT DISTINGUER LE PORTAGE INACTIF
DE L’HCA AgHBe LE SUIVI +++
10 10
10 9
10 8
10 7
10 6
10 5
10 4
10 3
10 2
10

Hé pat...
QUI TRAITER
Guidelines EASL
1. Indications semblables pour
HC AgHBe + ou AgHBe 2. Indication dépend de:
- ADN VHB
- ALAT
-...
QUI TRAITER
Guidelines EASL
AgHBe + et AgHBe -

EASL Clinical Practice Guidelines: Management of chronic hepatitis B.
J He...
QUI TRAITER
Guidelines EASL
AgHBe + et AgHBe -

ADN VHB < 4 log
ALAT = N

EASL Clinical Practice Guidelines: Management of...
QUI TRAITER
Guidelines EASL
AgHBe + et AgHBe -

ADN VHB < 4 log
ALAT = N

Surveiller
EASL Clinical Practice Guidelines: Ma...
QUI TRAITER
Guidelines EASL
AgHBe + et AgHBe -

ADN VHB < 4 log
ALAT = N

ADN VHB > 4 log
et/ou ALAT > N
PBH > A1/F1

Surv...
QUI TRAITER
Guidelines EASL
AgHBe + et AgHBe -

ADN VHB < 4 log
ALAT = N

Surveiller

ADN VHB > 4 log
Et/ou ALAT > N
PBH >...
COMMENT TRAITER
TREATMENT OF CHRONIC
HEPATITIS B
Two Strategies
- Analogues: pure antivirals
maintained response
- Interferon: antiviral +...
NUCs vs IFN
- Finite duration
- Sustained response
- No resistance
- Oral administration
- Good tolerance
- Low cost

NUCs...
RESULTS WITH ANALOGUES
VIROLOGICAL RESPONSE AT 1 YEAR
HBeAg-positive

HBeAg-negative
90% 88% 93%

100
Negative PCR
(%)

80

67%

60
40

73%

71%
...
ANALOGUES REGISTERED FOR THE
TREATMENT OF CHRONIC HEPATITIS B

- Lamivudine
- Adefovir
- Telbivudine

+

- Entecavir
- Ten...
ENTECAVIR
ENTECAVIR
ADN VHB NÉGATIF A 1 et 3-5
ANS
94%

94%

95%

55%

AgHBe +
.

Chan et al. Hepatology 2010

AgHBe -
ENTECAVIR DANS L’HC AgHBe +
ADN VHB négatif
100
80

85%

60
40

90%

91%

94%

55%

20
0

N=146
1 an

N=140
2 ans

N=134
3...
TENOFOVIR
TENOFOVIR
ADN VHB NÉGATIF A 1 et 5 ANS
93%
73%

87%*

65%*
*98%
Per protocol

AgHBe +

AgHBe -

.

Marcellin et al. NEJM 2...
Histologie à 5 ans de Traitement
n=348
100%

Ishak Fibrosis Score
6
5
4
3
2
1
0

s

90%
80%
70%
60%
50%
40%

i
f
o
g
a
t
n...
Cumulative incidence of HBV
resistance
100%

Year 1
Year 2
Year 3
Year 4
Year 5

90%
80%
70%

67%

70%

60%
49%

50%
40%
3...
NO CORRELATION BETWEEN ANTIVIRAL
POTENCY AND HBs SEROCONVERSION*
HBV DNA
decrease (log)

- Lamivudine
- Adefovir
- Entecav...
TREATMENT OF CHRONIC HEPATITIS B
WITH ANALOGUES: LIMITATIONS
- HBV DNA must be undetectable to prevent
resistance
- HBe se...
WHY HBsAg IS THE MAIN
OBJECTIVE OF THERAPY
THE IMPORTANCE OF HBsAg LOSS
- Ultimate goal of therapy
- Closest to cure
- Not HBV eradication but associated with
improv...
HBsAg AND THE RISK OF HCC
11,893 men in Taiwan

HBsAg
--+
+
+
+

HBeAg
----+
+

ALT
normal
elevated
normal
elevated
normal...
HBsAg Loss is Associated with Improved
Survival
309 cirrhotics with a mean follow-up of 6 years

Survival (%)

100
80
60

...
Cumulative Incidence of HBs

Seroconversion

INCIDENCE DE LA NÉGATIVATION DE L’AgHBs
EN FONCTION DE LA SÉROCONVERSION HBe
...
EVOLUTION (10 ans)
APRÈS TRAITEMENT IFN
AgHBs+ AgHBs• CHC :
• Ascite :
• Hemorhagie:
• Transplantation:
• Mortalité (CHC):...
RESULTS WITH INTERFERON
INCIDENCE OF HBsAg LOSS ACCORDING TO
RESPONSE TO IFN (HBe seroconversion)

1
,0
0
,8

Réponse : 64%

0
,6

p<.001

0
,4

S...
OUTCOME (10 years) AFTER IFN THERAPY
HBsAg+ HBsAg• HCC :
• Ascitis :
• Hemorhage:
• Transplantation:
• Mortality (HCC):

6...
PEG IFN
HBeAg negative CHB
HBsAg LOSS after PEG IFN ± LAM
11

12

9

%

5

0

6

1 an

2 ans

3 ans

Marcellin et al. NEJM 2004
Marcellin et al. Gast...
HBsAg LOSS

64% of the
patients HBV DNA
negative
12
11

9

%

5

0

6

1 an

2 ans

Marcellin et al. NEJM 2004
Marcellin e...
HOW TO TREAT
EASL Guidelines
HBeAg + or HBeAg -

• EASL Clinical Practice Guidelines: Management of chronic hepatitis B.
J...
HOW TO TREAT
EASL Guidelines
HBeAg + or HBeAg PEG IFN

HBV DNA < 7 log (copies)*
ALT > 3N

• 2 million IU
• EASL Clinical ...
HOW TO TREAT
EASL Guidelines
HBeAg + or HBeAg PEG IFN

HBV DNA < 7 log (copies)*
ALT > 3N

HBV DNA < 1 log at S12
• 2 mill...
HOW TO TREAT
EASL Guidelines
HBeAg + or HBeAg PEG IFN

ANALOGUE

HBV DNA < 7 log (copies)*
ALT > 3N

Entecavir or Tenofovi...
HOW TO TREAT
EASL Guidelines
HBeAg + or HBeAg PEG IFN

ANALOGUE

HBV DNA < 7 log (copies)*
ALT > 3N

Entecavir or Tenofovi...
HOW TO TREAT
EASL Guidelines
HBeAg + or HBeAg PEG IFN

ANALOGUE

HBV DNA < 7 log (copies)*
ALT < 3N

Entecavir or Tenofovi...
THE ROLE OF HBsAg
QUANTIFICATION
HBsAg ACCORDING TO TREATMENT
Weeks

Median log10 IU/mL

LAM
PEG-IFNα-2a
+ LAM
PEG-IFNα-2a

Treatment
Marcellin et al. Hepa...
HBsAg Kinetics: PEG IFN
SVR (+)

HBV DNA (Log10 copies/ml)

HBsAg (Log10 U/ml)

Treatment

Moucari et al. Hepatology 2009
HBsAg (Log10 U/ml)

HBV DNA (Log10 copies/ml)

HBsAg Kinetics: PEG IFN SVR (-)

Moucari et al. Hepatology 2009
Quantification of HBsAg: “Stopping Rule”
Early Serological Response = 0.5 log at W12
ESR +
48 Patients
treated with
PEG IF...
THE FUTURE OF THERAPY FOR HBV

PEG IFN + NUC
PEG IFN + LAM
SERUM HBV DNA
On-treatment
Mean HBV DNA (log10 cp/mL)

7
PEG IFN a2a
+ placebo

6
5

PEG IFN a2a
+ lamivudin...
PEG IFN + Telbivudine
HBsAg decline baseline to week 24

Baseline
PEG
42
LDT
46
LDT+PEG
16

Marcellin et al. Antiviral The...
PEG IFN + Tenofovir
- 36 patients
- 8 (22%) with HBsAg drop > 0.5 log at 24 weeks
- All with SVR
- 4 (11%) HBsAg negative ...
HBsAg kinetics according to treatment response
Log10 IU/ml

Marcellin et al. AASLD 2013
SVR patient with HBsAg loss
Log10 IU/ml

Marcellin et al. AASLD 2013
Conclusion
La quantification de l’AgHBs a une forte VPN:
- AgHBs à J0 > 3000 UI: 89%
- AgHBs diminué de moins de 0,5 log à...
PERSPECTIVAS
L’AVENIR?
PERSPECTIVAS

Traitement individualisé
Marcellin p  tt vhb 2014 final
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Marcellin p tt vhb 2014 final

  1. 1. TRAITEMENT DE L’HÉPATITE B Patrick Marcellin
  2. 2. L’HÉPATITE B EN FRANCE - 0,7% (300.000) porteurs chroniques* - 3ème cause de cirrhose et CHC - Mortalité: 1500/an** - < 150 000 dépistés - 15 000 traités - 1500 nouveaux traités par an * InVS 2005 ** INSERM CépiDC, FPRH, AFEF, InVS Marcellin et al. J Hepatol 2008
  3. 3. POURQUOI TRAITER?
  4. 4. OBJECTIFS DU TRAITEMENT DE L’HÉPATITE CHRONIQUE B? - 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
  5. 5. OBJECTIFS DU TRAITEMENT AgHBe ADN VHB négatif négatif Anti-Hbe Anti-HBs positif AgHBs positif négatif TEMPS
  6. 6. SEROCONVERSION HBs: LE CHAMPION DES CRITÈRES Seroconversion HBs ADN VHB négatif 3 Seroconversion HBe 1 2
  7. 7. QUI TRAITER
  8. 8. COMMENT OPTIMISER LE TRAITEMENT DE L’HÉPATITE CHRONIQUE B? -Traiter les malades qui en ont besoin (risque de complications) - Traiter les malades qui ont de bonnes chances de répondre
  9. 9. HEPATITE CHRONIQUE B = MULTIPLICATION VIRALE/RÉPONSE IMMUNITAIRE MULTIPLICATION VIRALE RÉPONSE IMMUNITAIRE
  10. 10. PHASE DE TOLÉRANCE IMMUNITAIRE = MAUVAISE RÉPONSE ADN VHB > 7 log AgHBe + MULTIPLICATION VIRALE ALAT < N PBH = A1F1 RÉPONSE IMMUNITAIRE
  11. 11. PHASE DE RÉACTION IMMUNITAIRE = BONNE RÉPONSE ADN VHB < 7 log AgHBe +/MULTIPLICATION VIRALE ALAT > N PBH > A1F1 RÉPONSE IMMUNITAIRE
  12. 12. CHARGE VIRALE ET STADE DE L’HC B 10 10 10 9 10 8 10 7 10 6 10 5 10 4 10 3 10 2 10 Hé patite chronique AgHBe Porteur inactif Martinot et al. J Hepatol 2002
  13. 13. COMMENT DISTINGUER LE PORTAGE INACTIF DE L’HCA AgHBe LE SUIVI +++ 10 10 10 9 10 8 10 7 10 6 10 5 10 4 10 3 10 2 10 Hé patite chronique AgHBe - Porteur inactif 1 2 Années 3 4 5 Asselah et al. GCB 2005
  14. 14. QUI TRAITER Guidelines EASL 1. Indications semblables pour HC AgHBe + ou AgHBe 2. Indication dépend de: - ADN VHB - ALAT - PBH EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2012
  15. 15. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2012
  16. 16. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - ADN VHB < 4 log ALAT = N EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2012
  17. 17. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - ADN VHB < 4 log ALAT = N Surveiller EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2012
  18. 18. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - ADN VHB < 4 log ALAT = N ADN VHB > 4 log et/ou ALAT > N PBH > A1/F1 Surveiller EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  19. 19. QUI TRAITER Guidelines EASL AgHBe + et AgHBe - ADN VHB < 4 log ALAT = N Surveiller ADN VHB > 4 log Et/ou ALAT > N PBH > A1F1 Traiter EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2012
  20. 20. COMMENT TRAITER
  21. 21. TREATMENT OF CHRONIC HEPATITIS B Two Strategies - Analogues: pure antivirals maintained response - Interferon: antiviral + immune modulator sustained response
  22. 22. NUCs vs IFN - Finite duration - Sustained response - No resistance - Oral administration - Good tolerance - Low cost NUCs +/+ + - IFN + + + +?
  23. 23. RESULTS WITH ANALOGUES
  24. 24. VIROLOGICAL RESPONSE AT 1 YEAR HBeAg-positive HBeAg-negative 90% 88% 93% 100 Negative PCR (%) 80 67% 60 40 73% 71% 60% 40% 51% 21% 20 0 ADV 1 LAM 2 ETV 3 LdT 2 TDF 4 1. Marcellin et al. N Engl J Med. 2003 3. Chang et al. N Engl J Med. 2006 5. Hadziyannis et al. N Engl J Med. 2003 ADV 5 LAM 2 ETV 6 LdT 2 TDF 4 2. Lai et al. N Engl J Med. 2007 4. Marcellin et al. N Engl J Med. 2008 6. Lai et al. N Engl J Med. 2006
  25. 25. ANALOGUES REGISTERED FOR THE TREATMENT OF CHRONIC HEPATITIS B - Lamivudine - Adefovir - Telbivudine + - Entecavir - Tenofovir +++ +++
  26. 26. ENTECAVIR
  27. 27. ENTECAVIR ADN VHB NÉGATIF A 1 et 3-5 ANS 94% 94% 95% 55% AgHBe + . Chan et al. Hepatology 2010 AgHBe -
  28. 28. ENTECAVIR DANS L’HC AgHBe + ADN VHB négatif 100 80 85% 60 40 90% 91% 94% 55% 20 0 N=146 1 an N=140 2 ans N=134 3 ans N=112 4 ans N=94 5 ans Chan et al. Hepatology 2010
  29. 29. TENOFOVIR
  30. 30. TENOFOVIR ADN VHB NÉGATIF A 1 et 5 ANS 93% 73% 87%* 65%* *98% Per protocol AgHBe + AgHBe - . Marcellin et al. NEJM 2008 Marcellin et al. Lancet 2013
  31. 31. Histologie à 5 ans de Traitement n=348 100% Ishak Fibrosis Score 6 5 4 3 2 1 0 s 90% 80% 70% 60% 50% 40% i f o g a t n c r e P 30% 20% 10% 0 Baselin e Year 1 Marcellin et al. Lancet 2013 Year 5
  32. 32. Cumulative incidence of HBV resistance 100% Year 1 Year 2 Year 3 Year 4 Year 5 90% 80% 70% 67% 70% 60% 49% 50% 40% 30% 38% 29% 24% 11% 10% 0% 22% 18% 20% 0% LAM 3% 0.2% 1.2% 1.2% 1.2% ADV ETV 4% 0% 0% 0% 0% 0% LdT TDF
  33. 33. NO CORRELATION BETWEEN ANTIVIRAL POTENCY AND HBs SEROCONVERSION* HBV DNA decrease (log) - Lamivudine - Adefovir - Entecavir - Telbivudine - Tenofovir * One year 5.0 4.0 7.0 6.5 5.5 ** Only in HBeAg- HBs loss 0% 0% 2%** 0% 3%**
  34. 34. TREATMENT OF CHRONIC HEPATITIS B WITH ANALOGUES: LIMITATIONS - HBV DNA must be undetectable to prevent resistance - HBe seroconversion inconstant despite virological response - Risk of resistance on the long term? - Tolerance on the long term? - Importance of compliance - When to stop? - HBsAg loss rare
  35. 35. WHY HBsAg IS THE MAIN OBJECTIVE OF THERAPY
  36. 36. THE IMPORTANCE OF HBsAg LOSS - 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
  37. 37. HBsAg AND THE RISK OF HCC 11,893 men in Taiwan HBsAg --+ + + + HBeAg ----+ + ALT normal elevated normal elevated normal elevated Relative Risk 1 5 10 30 60 110 Yang et al. NEJM 2002
  38. 38. HBsAg Loss is Associated with Improved Survival 309 cirrhotics with a mean follow-up of 6 years Survival (%) 100 80 60 HBsAg loss No HBsAg loss P<0.001 40 20 2 1 (years)3 Time 4 5 6 7 Fattovich et al. Am J Gastroenterology 1998
  39. 39. Cumulative Incidence of HBs Seroconversion INCIDENCE DE LA NÉGATIVATION DE L’AgHBs EN FONCTION DE LA SÉROCONVERSION HBe 1 ,0 0 ,8 64% 0 ,6 p<0,001 0 ,4 17% 0 ,2 0 ,0 0 5 1 0 1 5 T im ( ea ) e Y rs Moucari et al. J Hepatol 2009
  40. 40. EVOLUTION (10 ans) APRÈS TRAITEMENT IFN AgHBs+ AgHBs• CHC : • Ascite : • Hemorhagie: • Transplantation: • Mortalité (CHC): 6 5 0 0 4 0 0 0 0 0 Moucari et al. J Hepatol 2009
  41. 41. RESULTS WITH INTERFERON
  42. 42. INCIDENCE OF HBsAg LOSS ACCORDING TO RESPONSE TO IFN (HBe seroconversion) 1 ,0 0 ,8 Réponse : 64% 0 ,6 p<.001 0 ,4 Seroconversion 0 ,2 Non réponse : 17% Cumulative Incidence of HBsAg 0 ,0 0 5 1 0 1 5 T im (Y rs e ea ) Moucari et al. J Hepatol 2009
  43. 43. OUTCOME (10 years) AFTER IFN THERAPY HBsAg+ HBsAg• HCC : • Ascitis : • Hemorhage: • Transplantation: • Mortality (HCC): 6 5 0 0 4 0 0 0 0 0 Moucari et al. J Hepatol 2009
  44. 44. PEG IFN HBeAg negative CHB
  45. 45. HBsAg LOSS after PEG IFN ± LAM 11 12 9 % 5 0 6 1 an 2 ans 3 ans Marcellin et al. NEJM 2004 Marcellin et al. Gastroenterology 2009 Marcellin et al. Hepatology International. In press 4 ans 5 ans
  46. 46. HBsAg LOSS 64% of the patients HBV DNA negative 12 11 9 % 5 0 6 1 an 2 ans Marcellin et al. NEJM 2004 Marcellin et al. Gastroenterology 2009 Marcellin et al. APASL 2009 3 ans 4 ans 5 ans
  47. 47. HOW TO TREAT EASL Guidelines HBeAg + or HBeAg - • EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  48. 48. HOW TO TREAT EASL Guidelines HBeAg + or HBeAg PEG IFN HBV DNA < 7 log (copies)* ALT > 3N • 2 million IU • EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  49. 49. HOW TO TREAT EASL Guidelines HBeAg + or HBeAg PEG IFN HBV DNA < 7 log (copies)* ALT > 3N HBV DNA < 1 log at S12 • 2 million IU • EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  50. 50. HOW TO TREAT EASL Guidelines HBeAg + or HBeAg PEG IFN ANALOGUE HBV DNA < 7 log (copies)* ALT > 3N Entecavir or Tenofovir or Telbivudine HBV DNA < 1 log at S12 • 2 million IU • EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  51. 51. HOW TO TREAT EASL Guidelines HBeAg + or HBeAg PEG IFN ANALOGUE HBV DNA < 7 log (copies)* ALT > 3N Entecavir or Tenofovir or Telbivudine HBV DNA < 1 log at S12 • 2 million IU • EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  52. 52. HOW TO TREAT EASL Guidelines HBeAg + or HBeAg PEG IFN ANALOGUE HBV DNA < 7 log (copies)* ALT < 3N Entecavir or Tenofovir or Telbivudine HBV DNA < 1 log at S12 If HBV DNA + at S24-48 Change analogue • 2 million IU • EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009
  53. 53. THE ROLE OF HBsAg QUANTIFICATION
  54. 54. HBsAg ACCORDING TO TREATMENT Weeks Median log10 IU/mL LAM PEG-IFNα-2a + LAM PEG-IFNα-2a Treatment Marcellin et al. Hepatology International 2012
  55. 55. HBsAg Kinetics: PEG IFN SVR (+) HBV DNA (Log10 copies/ml) HBsAg (Log10 U/ml) Treatment Moucari et al. Hepatology 2009
  56. 56. HBsAg (Log10 U/ml) HBV DNA (Log10 copies/ml) HBsAg Kinetics: PEG IFN SVR (-) Moucari et al. Hepatology 2009
  57. 57. Quantification of HBsAg: “Stopping Rule” Early Serological Response = 0.5 log at W12 ESR + 48 Patients treated with PEG IFN a2a PPV = 89 % SVR Sustained VirologicalResponse ESR - NPV = 90 % Moucari et al. Hepatology 2009
  58. 58. THE FUTURE OF THERAPY FOR HBV PEG IFN + NUC
  59. 59. PEG IFN + LAM SERUM HBV DNA On-treatment Mean HBV DNA (log10 cp/mL) 7 PEG IFN a2a + placebo 6 5 PEG IFN a2a + lamivudine 4 – 4.1 3 – 4.2 – 5.0 2 0 6 Marcellin et al. NEJM 2004 12 18 24 30 36 42 48 Study week lamivudine 0.9 log
  60. 60. PEG IFN + Telbivudine HBsAg decline baseline to week 24 Baseline PEG 42 LDT 46 LDT+PEG 16 Marcellin et al. Antiviral Therapy 2013 Week 12 42 46 16 Time on treatment Week 24 42 46 16
  61. 61. PEG IFN + Tenofovir - 36 patients - 8 (22%) with HBsAg drop > 0.5 log at 24 weeks - All with SVR - 4 (11%) HBsAg negative at 24 weeks post-TX Marcellin et al. AASLD 2013
  62. 62. HBsAg kinetics according to treatment response Log10 IU/ml Marcellin et al. AASLD 2013
  63. 63. SVR patient with HBsAg loss Log10 IU/ml Marcellin et al. AASLD 2013
  64. 64. Conclusion La quantification de l’AgHBs a une forte VPN: - AgHBs à J0 > 3000 UI: 89% - AgHBs diminué de moins de 0,5 log à S24: 86% Ces résultats suggèrent qu’il est possible de sélectionner les bons répondeurs traitement et de considérer un arrêt à S24. avant
  65. 65. PERSPECTIVAS L’AVENIR?
  66. 66. PERSPECTIVAS Traitement individualisé

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