Download - Ratziu hepatite delta 2014
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Hépatite DeltaEpidémiologie, 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.
HDV+
(p<0.01)
73
56
%under40 yrs
HDV -
%withHDV
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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 8Overallprevalence %
% withHDV
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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
2001n=127
2002n=101
2003n=43
2004n=65
2005n=171
2006n=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 total12 G1; 1G6; 1G741% 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 inflammationMore frequent minimal cases
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Epidemiology of HDVSummary 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
HEPATOCELLULARCARCINOMA
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
%
Coinfection
Superinfection
Acute HBV
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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
SérologieAg 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 connusSeuil de sensibilité 100 copies/mL
PCR Quantitative:Technique maison « consensus » pour tous les génotypes connusSeuil de sensibilité 100 copies/mL - Linéarité: 103 à 109 copies/mL
Apport essentiel des techniques moléculaires
Intérêt secondaire des IgMMoins 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% Developedcirrhosis
Improved
Stable
Died
Complicated
Stable
NO CIRRHOSIS INITIALLYFollow-up: 4.1 y (n=75)
CIRRHOSIS INITIALLYFollow-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 riskof HCC 13 2 4occurrence (%)
(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
mildhepatitis
severehepatitis
histologicalcirrhosis
clinicalcirrhosis
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 casHBVDNA 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 fluctuants
Schaper J Hepatol 2010
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Virologic Correlates of Liver Disease Progression in HDV Superinfection
LOBULAR HEPATITIS
CAH CPHREMISSION
CIRRHOSISHCC
HDVRNA
HBVDNA
ALT
(Wu Gastroenterology 1995)
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Clinical course of HDV infection
cirrhosis Clinicaldecompensation
HCC
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’HDVL’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’HDVImportant 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’IFNa nécessaires (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 INTERFERONRESULTATS 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
00,5
11,5
22,5
33,5
9 MUI
3 MUI Pas de Trt
Score inflammation
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)Adefovir dipivoxil 10 mg daily
PEG-IFNa-2a (180 µg oiw)Placebo
PEG-IFNa-2a (180 µg oiw)Placebo
Adefovir dipivoxil 10mg dailyAdefovir 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)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)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)Patients (%) with negative HDV-RNA (ITT)
F24
TW48
PEG-IFN / ADVPEG-IFN / PADV
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)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 Pts1-2 ans TrtWithdrawal 16%SVR 19% (10-29%)
N=71 Pts1-1.5 ans TrtWithdrawal 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 S96 17,1 (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
Rechute 9/25(36 %)
7/18(39 %)
Négativation ARN VHD post-Trt 1 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)