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EPATITE B, UNA EPIDEMIA SCONOCIUTA
EPATITE B, UNA EPIDEMIA SCONOCIUTA
Maurizio KOCH
Azienda Ospedaliera San Filippo NeriU.O.C. Gastroenterologia ed Epatologia
Maurizio KOCH
Azienda Ospedaliera San Filippo NeriU.O.C. Gastroenterologia ed Epatologia
Hepatitis B VirusHepatitis B Virus
•Hepadnavirus
•100 volte più infettivo di HIV
•Si trova nel sangue e nei fluidi corporei
•Sopravvive più di 7 giorni nel sangue essiccato
•Hepadnavirus
•100 volte più infettivo di HIV
•Si trova nel sangue e nei fluidi corporei
•Sopravvive più di 7 giorni nel sangue essiccato
Host DNA
Different virus replication strategies
different treatment goalsHost cell
Nucleus
HBV HIV HCV
cccDNAProviral DNA
Viral RNA
TREATMENTTREATMENT TREATMENTLong-term reduction of viral replication to lowest possible level1
Lifelong suppression of viral replication2,3
Definitive viral clearance1
SVR possible for HCV1
1. Pawlotsky JM. J Hepatol 2006;44:S10-S13; 2. Siliciano JD, Siliciano RF. J Antimicrob Chemother 2004;54:6-9;
3. Lucas GM. J Antimicrob Chemother 2005;55:413-416cccDNA = covalently closed circular DNA
L’impatto della epatite B nel mondo è altoL’impatto della epatite B nel mondo è alto
Infetti presente/passato
Infezioni croniche
Morte
Causa di morte per malattia
Lavanchy D, J viral Hepatol 2004Conjeevaram HS, J Hepatol 2003
~ 2 miliardi
350-400 milioni
0.5-1.2 milioni/anno
10° causa nel mondo
Prevalenza HBsAg
≥ 8% = alta 2% - 7% = intermedia<2% = bassa
2 miliardi di HBV infetti 25 – 40% (75-160 M)/diedi cirrosi o HCC
WHO Fact SheetsConjeevaram HS, J hepatol 2003Lee WM N Engl J Med 1997Lok AS N Engl J Med 2002
6 miliardiPopolazione mondiale
350 - 400 milioni di Epatiti croniche HBV
IMPATTO GLOBALE DELL’EPATITE BIMPATTO GLOBALE DELL’EPATITE B
AA
F
A
E
D
DC
B
C
GG
HBV HBV genotypesgenotypes
H
Le dimensioni del Problema in ItaliaLe Le dimensionidimensioni del del ProblemaProblema in Italiain Italia
•Ogni giorno in Italia muoiono 57 persone per epatocarcinoma o cirrosi
–14 sono HBsAg+
•600.000 -1.000.000 di portatori cronici di HBV (HBsAg+)
•1034 nuove infezioni all’anno notificate e ~ 10.000 stimate (il numero effettivo di nuove infezioni per anno è 5-10 volte il numero di casi denunciati)
•250.000 portatori tra cittadini immigrati
••OgniOgni giornogiorno in Italia in Italia muoionomuoiono 57 57 personepersone per per epatocarcinomaepatocarcinoma o o cirrosicirrosi
––14 14 sonosono HBsAgHBsAg++
••600.000 600.000 --1.000.000 1.000.000 didi portatoriportatori cronicicronici didi HBV HBV ((HBsAgHBsAg+)+)
••1034 1034 nuovenuove infezioniinfezioni allall’’annoanno notificatenotificate e e ~~ 10.000 10.000 stimatestimate ((ilil numeronumero effettivoeffettivo didi nuovenuove infezioniinfezioni per per annoanno èè 55--10 10 voltevolte ilil numeronumero didi casicasi denunciatidenunciati))
••250.000 250.000 portatoriportatori tratra cittadinicittadini immigratiimmigratiWHO: Department of Communicable Diseases Surveillance and response 2002; AISF: AISF: documentodocumento conclusivoconclusivo commissionecommissione sullsull’’ epidemiologiaepidemiologia delledelle malattiemalattie epaticheepatiche
Il paziente con epatite cronica Il paziente con epatite cronica HBeAg HBeAg +: +: il ruolo della risposta immunitariail ruolo della risposta immunitaria
23456789
1
10
100
0
100
200
300
400
HB
V-D
NA
( log
10 g
en.E
q./m
l )
IgM
anti-
HB
c( P
EI
Uni
ts )
ALT
( U
/ L
)
HBeAg Anti- HBe
ImmuneImmune--tolerance tolerance ImmuneImmune--activation activation ImmuneImmune--controlcontrol
Association of Liver Disease with Virological/Biochemical
Parameters
Hu KQ, et al. 43rd EASL; Milan, Italy; April 23-27, 2008. Abstract 653.
p-value is based on a Fisher’s exact test
Normal Elevated Normal Elevated
Per
cent
of P
atie
nts
with
Act
ive
Live
r Dis
ease
p < 0.001
0102030405060708090
100
ALT (IU/L) AST (IU/L) HBV DNA(log10 copies/mL)
13.3%
35.5%
9.5%
57.9%
13.6 %
40.9%p = 0.088
p = 0.073
< 6.5 >6.5
EpatiteEpatitecronicacronica
CirrosiCirrosiEpatocarcinomaEpatocarcinoma
MorteMorte
EpatiteEpatiteacutaacuta
Primary HBV Primary HBV InfectionInfection
STORIA NATURALESTORIA NATURALE
STORIA NATURALESTORIA NATURALE
EpatiteEpatitecronicacronica
CirrosiCirrosi
EpatocarcinomaEpatocarcinoma
MorteMorte
EpatiteEpatiteacutaacuta
Primary HBV Primary HBV InfectionInfection
Subclinica
Epatiteacuta
EpatiteFulminante
0.1-0.5%
70-90%
10-30%
EpatiteEpatitecronicacronica
CirrosiCirrosiEpatocarcinomaEpatocarcinoma
MorteMorte
EpatiteEpatiteacutaacuta
Primary HBV Primary HBV InfectionInfection
STORIA NATURALESTORIA NATURALE
0.2% adulti immunocompetenti
95% neonati da madri HBsAg+/HBeAg+
23 – 28% bambini 1 – 5 anni
3% giovani 18 – 24 anni
STORIA NATURALESTORIA NATURALE
Epatite cronicalieve → moderata → grave
Epatite cronicalieve → moderata → grave
guarigioneguarigionecirrosicirrosi
morte / trapiantomorte / trapianto
scompensoscompenso EpatocarcinomaEpatocarcinoma
Portatoreinattivo
Portatoreinattivo
10 - 20 %10 - 20 % ~ 1 % x anno~ 1 % x anno
4-6 % per anno4-6 % per anno
Prevalenza dei diversi fattori eziologici in 9997 soggetti con epatopatia, Italia 2001
Prevalenza dei diversi fattori eziologici Prevalenza dei diversi fattori eziologici in 9997 soggetti con in 9997 soggetti con epatopatiaepatopatia, Italia 2001 , Italia 2001
HBsAg anche con altri fattori=13,4%HCV anche con altri fattori=69,9%Alcol anche con altri fattori=23,0%
Sagnelli et al. J. Med. Virol. 2005
HBsAg+HBsAg+ 10%10%
HCV+HCV+56,3%56,3%
AltroAltro12,7%12,7%
AlcolAlcol9,4%9,4%
Alcol+HCVAlcol+HCV11,6%11,6%
Anni
Dati ISTAT
05
1015202530354045
69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 9920
0020
01
Cirrosi
Tasso di mortalità (decessi per 100.000 abitanti) per Cirrosi ed HCC in Italia 1969-2001
TassoTasso didi mortalitmortalitàà ((decessidecessi per 100.000 per 100.000 abitantiabitanti) per ) per CirrosiCirrosi ed HCC in Italia 1969ed HCC in Italia 1969--20012001
HCC
Mor
tix
100.
000
Perchè vaccinare?Perchè vaccinare?
02468
101214
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
Vacc
inaz
ione
Ant
i-HB
V
Incidenza di epatite B in Italia.SEIEVA 1985-2003
Incidenza di epatite B in Italia.Incidenza di epatite B in Italia.SEIEVA 1985SEIEVA 1985--20032003
Stroffoni Hepatol 2000
Incidenza (per 100000) età specificadi epatite B in Italia. SEIEVA 1985-2003
Incidenza (per 100000) etIncidenza (per 100000) etàà specificaspecificadi epatite B in Italia. di epatite B in Italia. SEIEVA 1985SEIEVA 1985--20032003
Vacc
inaz
ione
Ant
i-HB
V
Stroffoni Hepatol 2000
05
1015202530354045
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
0-14
15-24
> 24
Perchèsottoporre a screening?Perchèsottoporre a screening?
Screening per epatite B: motivazioni
Screening per Screening per epatiteepatite B: B: motivazioni motivazioni
• precoce identificazione e cura dei soggettti infetti(Valla et al 2003)
• Prevenzione della diffusione ad altri soggetti (Valla et al. 2003)
• Terapie antivirali efficaci sono in grado di rallentarela progressione della malattia nei soggetti con epatite cronica B e ritardare l’insorgenza dellacirrosi (Liaw et al 2004)
• Per i pazienti con cirrosi in fase terminale l’unicapossibile terapia è il trapianto di fegato
Dove dovrebbe essere disponibile lo screenig per epatite B
Dove Dove dovrebbedovrebbe essereessere disponibiledisponibile lo lo screenigscreenig per per epatiteepatite BB
• Carceri• Strutture sanitarie ed in
particolare:– Centri per malattie
sessualmentetrasmissibili
– Centri per il trattamentodella dipendenza dasostanze d’abuso
– Centri trasfusionali– Centri per la terapia
dell’HIV
• Centri per immigrati• Agenzie internazionali
per l’adozione
Perchè trattare?Perchè trattare?
Survival in compensated cirrhosis BSurvival in compensated cirrhosis B
80 %84 %86 %
3 (1-7)4 (2-17)6 (1-16)
414648
7677161
AsiaEuropeEurope
Liaw 1989De Jong 1992Fattovich 2002
5-yearsurvival
Follow-upyrs (range)
Medianage (yrs)
Pts(n)
AreaReference
0 1 2 3 4 5 6 7 8 9 100
20
40
60
80
100%
HCC
survival
decompensation
86
68
16
30
918
Incidence100 person/yrs=3.5
Fattovich, Am J Gastroenterol 2002; 97: 2886-95
0 2 4 6 8 10 12
HBV DNA level log cp/mL
His
tolo
gyA
ctiv
ityIn
dex
2
4
6
8
10
12
From: Mommeja-Marin H, Hepatology. 2003.
Relazione tra livelli di HBV DNA e indice di attività istologica.
Una review di 26 studi prospettici
Relazione tra livelli di HBV DNA e indice di attività istologica.
Una review di 26 studi prospettici
Iloeje, Gastroenterology 2006
Relazione tra livelli di HBV DNA e sviluppo di cirrosi
Relazione tra livelli di HBV DNA e sviluppo di cirrosi
Clinical benefits of HBeAg and HBsAgclearanceClinical benefits of HBeAg and HBsAgclearance
HBsAg clearanceHBsAg clearance
Disease remissionHBsAg seroconversion
Prevention of HCC Increased survival
Disease remissionHBsAg seroconversion
Prevention of HCC Increased survival
Hoofnagle Ann Intern Med 1981; Fattovich Hepatology 1986;Di Bisceglie Gastroenterology 1987;Niederau NEJM 1996; Chu Gastroenterology 2002; van Zonneveld Hepatology 2004
HBeAg clearance HBeAg clearance
Fattovich et al. Am J Gastroenterol 1998
HBsAg clearance improves survival rates
HBsAg clearance improves survival rates
Probability of survival in patients with and without HBsAg clearance
0 2 4 6 8 10 12 14Years
No HBsAgclearance
20
40
60
80
100
Surv
ival
(%)
With HBsAgclearance
P<0.001
Retrospective study of 309 patients over mean follow-up of 5.7 years
0
20
40
60
80
100
0 12 24 36 48 60 72 84 96 108 120
Patients at risk
P<0.001
Treatment failure (71 pts)
Sustained response (30 pts)Pa
tient
sal
ive
and
com
plic
atio
ns-fr
ee(%
)
Months
30 30 30 30 30 28 1019 18 1371 68 64 59 45 36 528 21 15 4
3
Cumulative probability of complications-free survival in 101 HBeAg negative patients treated with IFN for 2 years
Cumulative probability of complications-free survival in 101 HBeAg negative patients treated with IFN for 2 years
Lampertico, Hepatol 2003
HCC: 7% vs 7%, NSDecompensation: 0% vs 27%, p<0.001
1
3
5
7
9
11
Patie
nts
with
HB
sAg
clea
ranc
e (%
)
3%
6%
8%
HBsAg clearance continues to increase after therapy in HBeAg-negative patients treated with
PEG-IFN
HBsAg clearance continues to increase after therapy in HBeAg-negative patients treated with
PEG-IFN11%
1 2 3 4Years after EOT
Marcellin et al. EASL 2008
n=230
1992 2008 and beyond…
interferon-alfa
adefovir telbivudinelamivudine
““The New EraThe New Era””ORAL Therapy
1998 2002
Therapy for Chronic Hepatitis B: 2008
2005
entecavir
pegylatedIFN-α
Tenofovir*
Combination Rx
2006
*FDA-approved for HIV and in review by FDA for HBV indication** in phase III trial
Lamivudine in compensated cirrhosisTime to diagnosis of HCC
Lamivudine in compensated cirrhosisTime to diagnosis of HCC
Placebo (n=215) Lamivudine (n=436)
Percentage with diagnosis
Time to diagnosis (months)
Lamivudine
Placebo
P=0.047
Excluding 5 cases in yr1: HR=0.47; P=0.052
Liaw et al, NEJM 2004
Resistance Rates in Naïve PatientsResistance Rates in Naïve PatientsGenotypic resistance to ADV4
HBeAgHBeAg((--) patients) patients
0 311 18
29
0
20
40
60
80
100
1 2 3 4 5Year of treatment
Cum
ulat
ive
of
resi
stan
ce (%
)
Colonno RJ, Hepatology. 2006; Zefix® (lamivudine) (August 2006) . Chang TT. J Gastroenterol Hepatol 2004; Hepsera® (August 2006) Standrigg DN, J Hepatol. 2006; Lai CL, Hepatology. 2006
Genotypic resistance to LVD2,3
100
Year of treatment0
20
40
60
80
1 2 3 4 5
Prev
alen
ce o
f re
sist
ance
(%)
242422404033
575733 676722
ND
HBeAgHBeAg(+) and ((+) and (--) patients) patients
Genotypic resistance to ETV1
0
20
40
60
80
100
1 2 3 4Year of treatment
Prev
alen
ce o
f res
ista
nce
(%)
<1% <1% 1%
5
ND1%
Monotherapy exerts pressure on replicating virus
Hypothetical representation based on information from Sarrazin C, et al. Gastroenterology 2007;132:1767-1777; Hinrichsen H, et al. Gastroenterology 2004;127:1347-1355
Selection of resistant variants
Wild-type STAT-C-resistant variant
Treatment end
Vira
l loa
d
Time
Treatment start
Potent viral load suppression with entecavir even from high
baseline levels
HBV DNA reductions by baseline DNA level2Nucleoside naïve, HBeAg(+) and (-) patients
³³ 1010 1111
1010 99
1010 88
1010 77
1010 66
1010 55
1010 44
1010 1010
Med
ian
HB
V D
NA
(Cop
ies/
mL)
Med
ian
HB
V D
NA
(Cop
ies/
mL)
1010 33
1010 22
2424 3636 4848 727200
n=13
n=27
n=82
n=97
n=144
n=151
n=40
n=87³³ 1010 1111
1010 99
1010 88
1010 77
1010 66
1010 55
101010 44
1010 1010
Med
ian
HB
V D
NA
(Cop
ies/
mL)
Med
ian
HB
V D
NA
(Cop
ies/
mL)
1010 33
1010 22
< 300 copies/mL
Treatment Week
2424 3636 4848 727200
n=13
n=27
n=82
n=97
n=144
n=151
n=40
n=87
1. Tenney DJ, et al. Antimicrob Agents Chemother. 2007;51:902–911. Colonno R. ISVHLD 2006; Oral presentation O200
• Average intracellular entecavir tri-phosphate drug concentrations are approximately 50 times greater than the IC50 of wild-type HBV1
Per
cent
age
(%)
0
10
20
30
40
50
60
70
80
90
100
Weeks on Study0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76
250TDF N= 250250 239239239 240240240 226226226125ADV N= 125125 121121121 117117117 111111111
Patients with HBV DNA <400 c/mL
Randomized Double Blind Open Label TDF
98%98%
P=0.983
Observed DataMarcellin P, et al. 43rd EASL; Milan, Italy; April 23-27, 2008. Abstract 57.
1. Lai CL et al. N Engl J Med. 2007;357:2576−2588; 2. Chang TT et al. N Engl J Med. 2006;354:1001−1010; 3. Lai CL et al. N Engl J Med. 2006;354:1011−1020; 4. Hadziyannis SJ et al. N Engl J Med. 2003;348:800−807;
5. Lai CL et al. N Engl J Med. 2006;354:1011−1020;6. Marcellin P et al. Hepatology. 2007;46 (S1):290-291A;
7. Globe study: data on file.
Data not from head-to-head studies. Design, inclusion and evaluation criteria may differ.HBV DNA thresholds: 1000 copies/mL (ADV); 300 copies/mL (LAM, LdT, ETV); 400 copies/mL (TDF)
−3.9 log −5 log−4.4 log −5.2 log
ADV2 LAM1 ETV3 LdT1
7.77.46.9
7.6
7
5
6
4
3
2
1
10
8
9
HBV DNA mean reduction at 1 yearHBeAg-negative patients
20
40
60
80
100
PC
R n
egat
ive
(%)
LAM1ADV4 ETV5 LdT1 TDF6
51%
71%
90% 88%93%
HBV DNA PCR negativity at 1 yearHBeAg-negative patients
HB
V D
NA
leve
l (lo
g c
op
ies/
mL
)
LdT7
95%
Efficacy Varies among Nucleos(t)ide Analogs
0123456789
Months
HB
V-D
NA
(log
cp/
ml)
ALT 206 60 25 40 426 182 40 41IgM anti-HBc 1.75 0.85 0.05 0.10 1.30 - 0.05 0.04
LLQ
LAM 100 mg/day
May 2003 – May 2005
0 2 4 6 8 10 12 14 16 18 20 22 24
ADV 10 mg/day
LLQ
O.DONNELL
E.A.R.L.Y. Study: Mean HBV DNA Change
Mea
n ch
ange
in H
BV D
NA
by P
CR
(lo
g 10
copi
es/m
L)
Weeks
*Primary efficacy end point: p<0.0001
– 4.42*
– 6.23*
– 5.08
– 7.28
– 5.96
– 7.82
0
2
4
6
8
10
12
0 8 16 24 32 40 48 56 64 72 80 88 96
Log10 300 copies/mL
Dosing through Week 48 Extended dosing phase
Leung N, et al. 43rd EASL; Milan, Italy; April 23-27, 2008. Abstract 998.
ETV (n=33) ADV (n=32)
Other Results at Week 96:Normal ALT: 97% vs. 85%HBe Seroconversion: 24% vs. 25%Discontinuation due to AE: 0% vs. 3%
Mean Change in HBV DNA
Hui et al. Hepatology 2007
0 20 40 60 80 100 120
Time (months)
Cu
mu
lati
ve p
rob
abili
ty o
f re
gre
ssio
n o
f fi
bro
sis
(%)
P<0.00005
Patients with sustained disease remission
Patients without sustained disease remission
Spontaneous HBeAg seroconversion: reduces fibrosis progression
Spontaneous HBeAg seroconversion: reduces fibrosis progression
100
80
60
40
20
0
Hsu et al. Hepatology 2002
Disease progression
0 2 4 6 8 10 12 14 16 18
Years after HBeAg seroconversion
Cu
mu
lati
ve in
cid
ence
of
cirr
ho
sis
(%)
HBeAg reversion
HBeAg-negative hepatitis
Sustained remission
Spontaneous HBeAg seroconversion: reduces incidence of cirrhosis
Spontaneous HBeAg seroconversion: reduces incidence of cirrhosis
100
80
60
40
20
0
Korevaar et al. AASLD 2007
HBsAg persistence (n=42)HBsAg clearance (n=20)
Fibrosis
%
PP<0.01<0.01
Histological outcomeHistological outcome
0
10
20
30
40
50
60
70
80
90
100
Improvement Stability Deterioration
Relazione tra decremento di HBV DNA terapiaindotto e miglioramento dell’istologia epaticaRelazione tra decremento di HBV DNA terapiaindotto e miglioramento dell’istologia epatica
Literature analysis of 26 prospective clinical studiesPredominantly Caucasian patient population
-2
1 2 3 54
4
3
2
1
0
-1 Median log10 HBV DNA level decrease from baselineMed
ian
hist
olog
icac
tivity
inde
xim
prov
emen
ts fr
om b
asel
ine
p<3x10-6r=0.96
Mommeja-Marin H, Hepatol 2003
Hepatitis B and risk of HCCHepatitis B and risk of HCC
Yang NEJM 2002
12
10
8
6
4
2
0
Perc
ent c
umul
ativ
e in
cide
nce
0 1 2 3 4 5 6 7 8 9 10Time (years)
HBsAg+, HBeAg+
HBsAg+, HBeAg–
HBsAg–, HBeAg–
Cumulative Hazards of Progression from Asymptomatic CHB to Chronic HepatitisCumulative Hazards of Progression from Asymptomatic CHB to Chronic Hepatitis
0 1 2 3 4 5 6 7 8 9 10 11 12 130.0
0.1
0.2
0.3
0.4
0.5
0.6
Year of follow-up
Cum
ulat
ive
Haz
ard
of C
hron
ic H
epat
itis
Chen JD, et al. 43rd EASL; Milan, Italy; April 23-27, 2008. Abstract 644.
HBeAg(+) HBV DNA ≥104
HBeAg(-) HBV DNA ≥104
HBeAg(-) HBVDNA <104
00.0
0.1
0.2
0.3
0.4
0.5
0.6
1 2 3 4 5 6 7 8 9 10Year of follow-up
Cum
ulat
ive
Haz
ard
of L
iver
Dis
ease
HBeAg(+) HBV DNA ≥104
HBeAg(-) HBV DNA ≥104
HBeAg(-) HBV DNA <104
Cumulative Hazards of Progression from Chronic Hepatitis to Cirrhosis
Cumulative Hazards of Progression from Chronic Hepatitis to Cirrhosis
Chen JD, et al. 43rd EASL; Milan, Italy; April 23-27, 2008. Abstract 644.
Il trattamento dell’epatite cronica BStresa 2007
Il trattamento dell’epatite cronica BStresa 2007
Lieve Moderata Grave Cirrosi Cirrosi scompensataLieve Moderata Grave Cirrosi Cirrosi scompensata
Interferone Peghilato (6-12 mesi)Interferone Peghilato (6-12 mesi)
Ishak: S2 S4 S6Ishak: S2 S4 S6
NUC (per 5 anni o 6 mesi success. perdita HBs)NUC (per 5 anni o 6 mesi success. perdita HBs)
HBeAg pos HBV DNA > 20.000IU/mL > 200 IU/mLHBeAb pos HBV DNA > 2.000IU/mL > 200 IU/mLHBeAg pos HBV DNA > 20.000IU/mL > 200 IU/mLHBeAb pos HBV DNA > 2.000IU/mL > 200 IU/mL
Treatment of chronic hepatitis BSummary
Treatment of chronic hepatitis BSummary
PegInterferon Lamivudine Adefovir Entecavir
Response in Yr 1HBe Ag+(seroconversion) 27% 16%-21% 12% 21%**HBe Ag+ (HBV DNA neg 1) 25% 40%-44% 40%* 67%**HBe Ag- (HBV DNA neg1) 63% 60%-70% 51% 90%***
Duration of treatmentHBe Ag+ 1 yr >1 yr >1 yr > 1yrHBe Ag- 1 yr >>1 yr2 >>1 yr2 >>1 yr2
Durability of response 3
HBe Ag+ 4 NA 50%-80% 91% 69%HBe Ag- 5 ~20% <10% ~5% NA
1 PCR assays * Ann Intern Med 2002 indefinite therapy ** NEJM 20063 24 weeks post-treatment *** NEJM 20064 HBe Ag seroconversion5 undetectable HBV DNA
Treatment of chronic hepatitis BSummary 2-5 yr
Treatment of chronic hepatitis BSummary 2-5 yr
PegInterferon Lamivudine Adefovir Entecavir
Response in Yr 2HBe Ag+(seroconversion) 12-14%* 11%***HBe Ag+ (HBV DNA neg1) 81%***HBe Ag- (HBV DNA neg1) 34%° 71%**
Response in Yr 5HBe Ag+(seroconversion) 50%§
HBe Ag+ (HBV DNA neg1)HBe Ag- (HBV DNA neg1) 67% §§
1 PCR assays ° Hepatol 2005* NEJM 2003** NEJM 2005*** NEJM 2006§ Gastroenterol 2003§§ Hepatol 2005
Decline of HBV cccDNA DuringLdT and LAM Therapy
• 38 patients on LdT and 32 patients on LAM
• Intrahepatic HBV DNA and cccDNA were measured by a previously validated real-time PCR assay
• Greater reduction of HBV DNA with LdT; no differences in CCC or intrahepatic DNA between groups
Wong DKH, et al. 43rd EASL; Milan, Italy; April 23-27, 2008. Abstract 1002.
*
-7
-6
-5
-4
-3
-2
-1
0HBV DNA
ChangeIntrahepatic HBV DNA
ccc DNA
LdTLAM
Log 1
0c/
mL