Ratziu hepatite delta du 2015
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Hépatite Delta
Epidémiologie, Histoire Naturelle
Vlad Ratziu
Hôpital Pitié Salpêtrière, Paris
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Epidemiology of HDV
Infection
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Introduction
Smallest hepatitis virus using HBs Ag as an
envelope (defective virus)
Only occurs in association with HBV
infection
Discovered in 1977, contagious
Modifies natural history of HBV infection
by aggravating pre-existent hepatitis or
creating hepatitis delta in healthy HBV
carriers
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Répartition géographique de l’infection chronique par HBV
2 à 7% - moyenne
> 8% - forte
< 2% - faible
Prévalence de l’AgHBs
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Prévalence de l’infection par HDV
Faible endémie Endémie Moyenne Forte endémieTrès faible endémie< 10% 10 à 20% 20 à 60% > 60%
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Epidemiological Patterns of
HDV Infection
Endemic:
– Southern Italy, Greece, Middle East, Mauritania,
Romania
Sporadic:
– Western countries
– Taiwan
Epidemic:
– Outbreaks in high risk communities (IV drug users)
– Venezuelan Basin of the Amazon (Santa Marta)
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Geographical Heterogeneity of
Anti-HDV Prevalence
Southern Italy : 23
Greece : 27
Taiwan : 15
Spain : 10
USA : 5
Alaska, Far East : 1-3
South Africa : 0
% of HBsAg carriers
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Age Specific Prevalence of HDV in 1556
Italian HBsAg Carriers (Sagnelli, J Hepatol 1992)
0
5
10
15
20
25
30
35
0-19 20-29 30-39 40-49 >50 yrs.
(p<0.01)
73
56
%
under
40 yrs
%
with
HDV
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8 HDV genotypes
Gen 1 : worldwide distribution, most
prevalent, severe disease, lower emission
Gen 2, 4 : Far East Asia, milder forms
(exceptions)
Gen 3 : South America, asso HBV gen F,
fulminant/severe hepatitis
Gen 5 to 8 : Africa
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HDV Routes of Infection
IV drug abuse +++
Household contact +++
Heterosexual contact +++
Homosexual contact +
Needles +
Vertical exceptional
Nosocomial exceptional
Multiple transfusions exceptional
Frequency
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Risk Groups for Delta Infection
Drug addicts +++
Heterosexual contacts of Delta infected
patients +++
Household contacts of Delta infected +++ Homosexual men
Multiple transfusion recipients, hemophiliacs
Other (health care workers, patients undergoing
hemodialysis, institutionalized patients)
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Geographical Variability of
HDV Risk Groups
Italy, Greece : Household contact
USA, Western Europe : IV Drug users
Taiwan : Heterosexual contacts
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Intrafamilial / Inapparent Parenteral
Transmission Cofactors
OR (C.I. 95%)
Household contact 12.9 (4-34)
with HDV carrier
Household > 6 1.9 (1.1-3.6)
Age 30-39 2.5 (1.4-4.5)
South vs. North 1.6 (1.1-2.5)
IV Drug abuse 8.4 (4.4-16)
(Sagnelli, J Hepatol 1992)
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Sexual Transmission of HBV
Heterosexual +++
Homosexual +/-
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Epidemiology of HDV
Infection
Current Trends in the 90’s :
a decline in HDV prevalence
3.1/100000 to 1.2/100000
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Decline in anti-HDV rate in
HBsAg carriers, Italy
0
5
10
15
20
25
30
1983 1987 1992 1997
%
23
14
8
25
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Declining Prevalence of HDV in Turkey
0
5
10
15
20
25
30
35
40
45
HBV with CLD HBV with cirrhosis
1980 2005
43 31 24 11
Degertekin, Turk J Gastroenterol 2006
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Decline of Acute HDV Infection in
Taiwan 1983-1996 (Huo, J Gastro Hepatol 1997)
0
5
10
15
20
25
83 86 89 92 95 88 91 96 year
Anti-HDV in
HBsAg carriers
HBsAg in
prostitutes
p<0.001 p<0.02%
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Age-specific Prevalence of anti-HDV
in HBsAg Carriers (Gaetta, Hepatology 2000)
0
5
10
15
20
25
30
0-29 yrs
30-49 yrs
> 50 yrs
199719921987
23 14 8Overall
prevalence %
% with
HDV
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Reasons for Decline in HDV
Endemicity
Global reduction of HBV infection :
– control of AIDS
– HBV vaccines
Reduction of inapparent/intrafamilial spread :
– improvement in economy, hygiene, living
conditions, reduced size families
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The decline in HDV does not
continue
London (UK) : 8.5%, stable 2000-2006
Hannover (Germany) : 6.8% in 1997; 8-
14% 2007- present
Italy : 8% in 2006
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Janvier 2003 - Août 2006
650 échantillons
HDV-8 (0.5%)HDV-6 (2%)
HDV-5 (15.5%)
HDV-7 (3.5%)
HDV-1 (78.5%)
Epidémiologie de HDV en France (CNR)
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Europe de l’Ouest :FranceItalieEspagneSuissePortugal
Inconnu
Asie :MongolieVietnam
Europe de l’Est :RoumanieRussieMoldavieTurquieSerbieBulgarieGeorgieKosovo
Afrique :Afrique du SudAlgérieAngolaBéninBurkina FasoCamerounCap VertComoresCongo (Brazzaville)Cote d’IvoireÉgypteGabonGambieGhanaGuinéeMadagascarMaliMarocMauritanieMayotteNigerNigeriaRépub.CentrafriqueRépub. D. CongoSénégalTchadTunisie
Evolution de l’origine géographique des patients infectés par
HDV entre 2001 et 2006
2001
n=127
2002
n=101
2003
n=43
2004
n=65
2005
n=171
2006
n=110
10%
20%
30%
40%
50%
60%
70%
80%
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Prevalence of HDV/HBV in asymptomatic blood donors in France
2% de séropositivité au total
12 G1; 1G6; 1G7
41% Afrique, 17% Bassin méditerranen
1.1% 1997-2005
4.2-6.5%
0.85%
Servant-Delmas J Inf Dis 2013
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Hepatitis Delta in Greece
• Prevalence : stable 1997-2010, 4.2%
• Lower in natives (2.8%) than in migrants
(7.5%)
• High in children
• Underreported (only 3% of HBsAg
tested)
Manesis, J Hepatol 2013
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The decline in HDV does not
continue …
2 pools in Western Countries
Residual ageing domestic
pool surviving the 70s-80s
epidemics
Young migrants from HDV
endemic areas with recent
HDV infectionLess florid forms of chronic active hepatitis
More indolent cirrhosis residual to burned-out inflammation
More frequent minimal cases
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Epidemiology of HDV
Summary and Conclusions
Varies unpredictably in incidence and pattern irrespective of HBV prevalence
Decreasing prevalence in recent years: HBV vaccine and/or economy
Prospects of changing prevalence due to mass migration (developing countries+++)
New foci: Russia (Caucasian republics), Albania, Northern India, Japon (Okinawa), South America
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Clinical Impact of HDV
Infection
Acute HDV Infection
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Hepatitis Delta : Clinical Aspects
Acute Hepatitis Delta
– Co-infection : acute HDV + acute HBV
– Super-infection : acute HDV on chronic HBV
Chronic Hepatitis Delta
– chronic HDV on chronic HBV
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HBsAg
HDVRNA
anti-HBs
ALT
anti-HDV
IgM anti-HDV
2 3 4 6 months
Acute HBV-HDV Coinfection
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HBsAg
HDVRNA
ALTanti-HDV
IgM anti-HDV
Acute and Chronic HBV-HDV
Superinfection
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Outcome of Acute HDV
COINFECTION SUPERINFECTION
Fulminant Recovery
Chronicity Chronicity
Recovery Fulminant
CIRRHOSIS
HEPATOCELLULAR
CARCINOMA
2-20%10-20%
90-95%5-10%
2-7% 90-95%
70-80%
40%??
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Acute HDV Infection
HBV infection acute chronic
Mortality rate 1-2 % 1-5 %
Chronicity rate 2-7 % 70-90 %
HBsAg transient persists
anti-HBc IgM positive negative
anti-HDV IgG delayed persists high
anti-HDV IgM transient persists
Biphasic ALT yes no
CO-INFECTION SUPERINFECTION
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Outcome of Acute HDV Infection
(Caredda J Inf Dis 1985)
0
5
10
15
20
Coinfection (n=86) 0
Super- 95
infection (n=21)
Acute HBV (n=50) 2
%
% OF SEVERE HEPATITIS
% OF CHRONICITY
%
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Influence of HDV on Severity of Acute
Hepatitis B (Smedile Lancet 1982)
Govindarajan Gastroenterology 1984)
N
Europe 111
Los Angeles 71
Europe 532
Los Angeles 118
FULMINANT
BENIGN
EUROPE LOS ANGELES
p<0.01 p<0.01
0
5
10
15
20
25
30
35
40
% anti-HDV
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Diagnostic de l’Hépatite delta
MARQUEURS DISPONIBLES
Sérologie
Ag delta sérique (pas de valeur diagnostique)
Ac anti-delta totaux (dépistage)
IgM anti-delta (infection aiguë, réplication)
Marqueurs moléculaires (techniques « maison »)
Recherche qualitative de l’ARN delta (sérum)
Quantification de l’ARN delta (sérum)
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Infection aiguë résolutive
IgM anti-Delta
IgG Anti-HD
Hépatite aiguë
ARN Delta
Ag Delta
Primo-infection
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IgM anti-Delta
Hépatite aiguë
IgG Anti-HD
ARN Delta
Primo-infection Hépatite chronique
Infection chronique
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Diagnostic de l’hépatite delta aiguë
- Ag HBs Positif
- Ac anti-delta total
- Ig M anti-delta +
- ARN viral: positif
- si coinfection: IgM anti-HBc +
- si surinfection: IgM anti-HBc -
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Marqueurs du suivi thérapeutique
PCR Qualitative (à Avicenne) :
Technique maison « consensus » pour tous les génotypes connus
Seuil de sensibilité 100 copies/mL
PCR Quantitative:
Technique maison « consensus » pour tous les génotypes connus
Seuil de sensibilité 100 copies/mL - Linéarité: 103 à 109 copies/mL
Apport essentiel des techniques moléculaires
Intérêt secondaire des IgM
Moins sensible que la PCR (faux négatifs) et moins spécifique de la
réplication virale (faux positifs)
Kits ELISA commerciaux
Suivi quantitatif de l’Ag HBs - en cours d’évaluation
Recherche de l’ARN viral intra-hépatique
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Clinical Impact of HDV
Infection
Chronic HDV Infection
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Histological Findings in Chronic
Hepatitis Delta, 1976-1981(Rizzetto Ann Intern Med 1983)
Normal or minimal changes : 0 %
Chronic Hepatitis : 100 %
– persistent hepatitis 8 %
– active hepatitis 70 %
– cirrhosis 22 %
Northern Italy ; N=137 of 568 HBsAg carriers (24%)
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Outcome in Chronic Hepatitis Delta(Rizzetto Ann Intern Med 1983)
31%
23%
46%45%
43%
12% Developed
cirrhosis
Improved
Stable
Died
Complicated
Stable
NO CIRRHOSIS INITIALLY
Follow-up: 4.1 y (n=75)
CIRRHOSIS INITIALLY
Follow-up : 3.7 y (n=26)
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Impact of HDV on HBV
Cirrhosis (Fattovich, Gut 2000)
Uncomplicated, Child A, untreated cirrhosis
White Europeans
Median follow-up 6.6 years
Prevalence of HDV : 20 %
N= 200; multicentric, European (Eurohep)
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Impact of HDV on HBV Cirrhosis
Faster progression to cirrhosis (younger age :
34 vs 48 years)
Increased risk of hepatocellular carcinoma
RR 3 (CI : 1-10), of decompensation and of
mortality (RR=2, n.s.)
HDV-/HDV-/
HDV+ HBeAg+ HBeAg-
5-year risk
of HCC 13 2 4
occurrence (%)(Fattovich, Gut 2000)
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Clinical Impact of HDV
Infection
Current Trends in the 90’s
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Trends in Histological/Clinical Severity
of Chronic HDV (Rosina, Gastroenterology 1999)
1977-1986 1987-1996
mild
hepatitis
severe
hepatitis
histological
cirrhosis
clinical
cirrhosis
8
17
31
446
65
28
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Réplication respective des virus
B et Delta
41%
32%
16%
11%B+/D+
B-/D+
B+/D-
B-/D-
PCR VHD pos ds 73% des cas
HBVDNA médian 3.4 log
(<2.5-8.6)
39 sujets coinfectés VHB-VHD
Schaper J Hepatol 2010
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Dynamic profiles of HDVRNA and
HBVDNA
Delta prédominant : 55% des cas
HBV prédominant : 30%
HBV et Delta activité similaire : 15%
PROFILS EVOLUTIFS
Activité persistante (des 2 ou 1 des 2)
Activité fluctuante (des 2 ou 1 des 2)
Les taux peuvent être très fluctuantsSchaper J Hepatol 2010
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Virologic Correlates of Liver Disease
Progression in HDV Superinfection
LOBULAR
HEPATITIS
CAH CPH
REMISSION
CIRRHOSIS
HCC
HDVRNA
HBVDNA
ALT
(Wu Gastroenterology 1995)
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Clinical course of HDV infection
cirrhosis Clinical
decompensationHCC
rate 2.7%/yr rate 2.8%/yrrate 4%/yr
Clinical decompensation and not HCC was the first complication of
cirrhosis to occur
HDV replication was an independent predictor of mortality and
cirrhosis occurrence and decompensation. Romeo, Gastroenterology 2009
299 cases, 1978-2006, mean follow-up 17 years
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Hepatitis Delta in Greece
• Prevalence : stable 1997-2010, 4.2%
• Lower in natives (2.8%) than in migrants
(7.5%); high in Children
• Underreported (only 3% of HBsAg
tested)
• Aggressive disease: more frequent
cirrhosis at a younger age
• Cirrhosis in the young adult
Manesis, J Hepatol 2013
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Impact Pathogène des Génotypes du
VHD
194 pts consécutifs avec hépatite BDelta
HF, Hep aigue, Hep Chr, Cirrhose, CHC
Genotype I du VHD plus mauvais Ptic que GII:
– + d’HF; + de CHC; + de morbimortalité hépatique
– - de rémission
La réplication active des 2 virus augmentait le
risque d’événements hépatiques
Su, Gastroenterology 2006
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TRAITEMENT DE
L’HEPATITE CHRONIQUE
DELTA
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0
10
20
30
40
50
60
70
80
90
Traitement par l’IFNa de l’HDV
L’Effet Antiviral est Dose Dépendant
27
45
71
36
0
Rosina 1991
3M Nontraites
9M 3M Nontraites
%PCRneg Farci, 1994
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Traitement par l’IFNa de l’HDV
Important Taux de Rechute a l’Arrêt
0
10
20
30
40
50
60
70
80
90
25
3
71
4336
0
%ALT=N
Fin Trt (12m)
Fin Suivi (32m)
Rosina 19913M; N=31
Farci 19949 M; N=14
Farci 19943 M; N=14
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Traitement par l’IFNa de l’HDV
Réponse retardée (plusieurs mois voire un an de traitement): traitement d’au moins un an
Relation dose-réponse: doses fortes d’IFNanécessaires (9MUI x 3/sem)
Taux élevé de rechute à l’arrêt: traitement prolongé?
Facteurs prédictifs de réponse non identifiés
Amélioration histologique même en l’absence de réponse virologique (57% groupe traité, 36% groupe non traité, Rosina, Hepatology 1991)
Cas décrits de disparition de l’AgHBs
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Traitement par l’IFNa de l’HDV
Etude randomisée italienne
– 14 pts 9 MUI x 3/sem , 48 sem
– 14 pts 3 MUI x 3/sem, 48 sem
– 14 pts non traités
Ag HBe : 88%
Cirrhose : 62%, HCA modérée à sévère : 17%
Suivi moyen post traitement 32 mois
Farci, N Engl J Med 1994
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TRAITEMENT PAR INTERFERON
RESULTATS EN FONCTION DE LA DOSE
Fin du traitement 6 mois après
ARN Delta négatif ARN Delta négatif
Non
traités 0% 8%
3 MU 36% 14%
9 MU 71% 43%
Farci, N Engl J Med 1994
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Amélioration Histologique sous
Traitement
• Amélioration nécrose periportale, inflammation et
nécrose lobulaire
• Différences significatives entre forte dose et non traités
-2
-1,5
-1
-0,5
0
0,5
1
1,5
2
2,5
3
3,5
9 MUI
3 MUI Pas de Trt
Score
inflam
mation
Farci, N Engl J Med 1994
9 MU
PLB
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Effets à Long Terme de l’IFNa
• Meilleure survie
• Meilleure survie sans TH
• Moins de complications
hépatiques graves
Farci, Gastroenterology 2004
Suivi moyen 12 ans
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Effets à Long Terme de l’IFNa à Forte Dose
chez les Répondeurs Biochimiques
Amélioration de la fonction hépatique
Baisse significative de la charge virale
moyenne
Perte tardive de l’IgM HDV (7 ds. 9MUI vs 2
ds 3MUI et 0 non Trt)
HDVRNA indétectable ds 3 cas (vs. 1 et 0)
avec disparition AgHBs dans 2 cas (vs. 1 et 0)
Farci, Gastroenterology 2004
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Effets à Long Terme de l’IFNa à Forte Dose
chez les Répondeurs Biochimiques
Amélioration de la fonction hépatique et de l’histologie (fibrose)
Baisse significative de la charge virale moyenne
Perte tardive de l’IgM HDV (7 ds. 9 MUI vs 2 ds 3 MUI et 0 non Trt)
HDVRNA indétectable ds 3 cas (vs. 1 et 0) avec disparition AgHBs dans 2 cas (vs. 1 et 0)
Farci, Gastroenterology 1994
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Traitement Prolongé anti-HDV :
la Guerre d’Usure
Homme 42 ans; hépatite aigue Dec 1981
Avril 1983: ALT 1000; AgHBs et anti-HDV
1 an de suivi ; ALT 200-800; 1984: cirrhose active
1 an de trt 5MUI/j; réponse ALT, amélioration inflammation
Retraitement IFN 5 MUI/j pdt 12 ans…!
PBH à 3.5 ans: fibrose en pont
A 6-7 ans: ALT N prolongé; à 10 ans HDVRNA neg prolongé; PBH F0; PCRB neg; seroconversion s
Effet secondaire: cheveux fins +++
Lau, Gastroenterology 1999
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Efficacité Virologique de l’Interféron
dans l’Hépatite Chronique B
Farci , Hepatology 2006
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Cinétique Virale du VHD sous
PegIFN
La quantification de l’ARNVHD est un marqueur de réponse virologique; elle identifie les répondeurs « rapides » et les « lents ».
Castelnau , Hepatology 2006
Répondeurs Rechuteurs Non-Répondeurs
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H. Wedemeyer –Delta Hepatitis 2009
A Multicenter Randomised Study Comparing the Efficacy of
Pegylated interferon-alfa-2a plus Adefovir dipivoxil
vs.
Pegylated interferon-alfa-2a plus Placebo
vs.
Adefovir dipivoxil
for the Treatment of Chronic Delta Hepatitis
“The HIDIT-1 Study”
Heiner Wedemeyer*, Cihan Yurdaydın*,
G. Dalekos, A. Erhardt, Y Çakaloğlu, H. Değertekin, S. Gürel,
S. Zeuzem, K. Zachou, H. Bozkaya, T. Bock, H.P. Dienes,
Michael P. Manns
for the Hep-Net/International Delta Hepatitis Study Group
*C. Yurdaydın and H. Wedemeyer contributed equally
funded by
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H. Wedemeyer –Delta Hepatitis 2009
The Hep-Net/International Delta Hepatitis
Intervention Trial (HIDIT-1)
PEG-IFNa-2a (180 µg oiw)
Adefovir dipivoxil 10 mg daily
PEG-IFNa-2a (180 µg oiw)
Placebo
Adefovir dipivoxil 10mg daily
TW0 TW24 TW48 F24Screening
N=32*
N=29
N=30
N=91
* 1 patient withdrew informed consent after randomization
Wedemeyer, N Engl J Med 2011
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H. Wedemeyer –Delta Hepatitis 2009
Significant decline of HDV-RNA with PEG-IFN
2
3
4
5
6
TW0 TW24 TW48 F24
HDV-RNA (copies/ml)
ADV
PEG-IFN / P
PEG-IFN / ADV
**
**
*
*p<0.02 vs TW0; ** p<0.001 vs. TW0 Wedemeyer, N Engl J Med 2011
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H. Wedemeyer –Delta Hepatitis 2009
PEG-IFN leads to sustained suppression
of HDV-RNA in about 25% of patients
2
3
4
5
6
TW0 TW24 TW48 F24
Median HDV-RNA levels (copies/ml)
ADV
PEG-IFN / P
PEG-IFN / ADV
0 10 20 30 40 50 60
Patients (%) with
negative HDV-RNA (ITT)
F
24
TW
48
PEG-IFN / ADV
PEG-IFN / P
ADV
Wedemeyer, N Engl J Med 2011
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H. Wedemeyer –Delta Hepatitis 2009
PEG-IFN & ADV combination resulted in a more
pronounced decrease of HBsAg levels
2,5
3
3,5
4
4,5
5
W0 W24 W48 F24
ADV
PEG-IFN / P
PEG-IFN / ADV
HBs-Ag (IU/ml)
Clearance of HBs-Ag in 2 patients treated with PEG-IFN & ADV
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Metanalyse PegIFN, IFN dans HDV
(hétérogénéité des études, du design)
N=156 Pts
1-2 ans Trt
Withdrawal 16%
SVR 19% (10-29%)
N=71 Pts
1-1.5 ans Trt
Withdrawal 11%
SVR 29% (19-41%)
2 ans pas mieux qu’un an
Alavian J Res Med Sci 2012
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Hépatite Delta - PEG-IFN 96 semaines : pas de bénéfice de la combinaison avec TDF (1)
• Etude HIDIT-2 randomisée contrôlée, multicentrique internationale (Allemagne, Turquie, Roumanie, Grèce)
• 120 patients B/D, 50 % naïfs de traitement,17 % AgHBe+, 45 % F4,
• ARN VHD médian 5,15 log10 c/ml, ADN VHB médian : 2,65-2,70 log10 UI/ml
• Titre AgHBs médian : 3,94-3,91 log10 UI/ml
Le PEG-IFN et le TDF sont bien tolérés chez les patients VHB/VHDWedemeyer H, Allemagne, AASLD 2013, Abs. 31, actualisé
Schéma de l’étude
PEG-IFN
+ TDF
PEG-IFN
+ placebo
Arrêt Trt 13/59 8/60
Décès 1/59 1/60
EIG 34 % 28 %
EIG/Trt 27 % 11 %
Pic ALAT* 19 % 18 %
Tolérance
* >10 x LSN ou > 2 x ALAT initiale
PEG-IFNα-2a 180 μg/sem.
+ tenofovir (TDF) 245 mg/j
PEG-IFNα-2a 180 μg/sem
+ placebo
Suivi
5 ans
Suivi
5 ans
96 semaines
S96 S120
(n = 59)
(n = 61)
R
76
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Hépatite Delta - PEG-IFN 96 semaines : pas de bénéfice de la combinaison avec TDF (2)
Efficacité comparable des deux traitements Wedemeyer H, Allemagne, AASLD 2013, Abs. 31, actualisé
ARN VHD indétectable Diminution titre AgHBs
> 0,5 log10 UI/ml
Réponse jusqu’à S96
(%)
S960
20
40
60
80
47
33
p = 0,10
Initial S12 S24 S48
PEG-IFN + TDF PEG-IFN + placebo
Perte AgHBs : 3/59 (5,1%)
Perte AgHBs : 5/61 (8,2%)
(%)
S960
20
40
60
80
Initial S12 S24 S48
3228
77
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Hépatite Delta - PEG-IFN 96 semaines : pas de bénéfice de la combinaison avec TDF (3)
Wedemeyer H, Allemagne, AASLD 2013, Abs. 31, actualisé
Facteurs initiaux prédictifs de la réponse à S96
(négativation ARN VHD)
Variable RR (IC 95 %) p
Sexe (F vs H) 2,38 (1,05-5,39) 0,037
ARN VHD initial 0,49 (0,33-0,72) < 0,001
Titre AgHBs initial 0,42 (0,19-0,9) 0,027
Diminution titre AgHBs
> 0,5 log10 UI/l jusqu’à S9617,1 (5,9-49,4) < 0,001
78
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Hépatite Delta - PEG-IFN 96 semaines : pas de bénéfice de la combinaison avec TDF (4)
Plus d’un tiers des patients ont une rechute 6 mois après l’arrêt
Wedemeyer H, Allemagne, AASLD 2013, Abs. 31, actualisé
RVS24 (S120)
29
(%)
0
20
40
60
80
p = 0,34
S96 S120
21
33
47
PEG-IFN
+ TDF
PEG-IFN
+ placebo
Rechute9/25
(36 %)
7/18
(39 %)
Négativation ARN
VHD post-Trt1 6
79
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H. Wedemeyer –Delta Hepatitis 2009
Wedemeyer Manns, Nat Rev Gastro 2010
Suggested treatment algorithm for Hepatitis Delta
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Traitement Hépatite Delta
IFN conventionnel: effet dose-durée
Bon nombre de réponses virologiques dans la deuxième année de trt (Gunsar Antiviral Ther 2005)
Rechutes à l’arrêt
Réponse retardée même après fin du trt
Améliore pronostic à long terme et la survie
Seroconversion AgHBs rare mais suivi trop court
Pas d’efficacité de la ribavirine; efficacité absente ou marginale de la lamivudine seule (Niro, Alim Pharmacol Ther 2005)
Intérêt de la clévudine?
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Traitement Hépatite Delta
PEGIFN efficacité chez 20-40% selon gravité maladie du foie
Fibrose peu sévère et malades naïfs : plus d’effet
Si bien toléré continuer (PEG)IFN jusqu’à disparition HDVRNA et AgHBs
Pour améliorer l’observance ajuster les doses individuellement après M12
L’IFN (PEG) devrait être essayé chez la plupart des pts avec maladie compensée (Farci, Hepatol 2006)