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Viral hepatitis in reproductive health
Pi= erre Jean Malè
Training in Reproductive Health <= /i>Research - Geneva 2006=
15.03.2006
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0115.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
HBV and HCV treatment
Pierre-Jean Malè MD
15.03.2006
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WHO and CDC Fact Sheets<= span lang=3DEN-GB style=3D'font-family:"MS PGothic";mso-ascii-font-family:Arial; mso-fareast-font-family:"MS PGothic";mso-hansi-font-family:Arial;font-size: 58%;mso-special-format:lastCR;display:none'>
Global Impact of Hepatitis B<= /div>
World population
6 billion
2 billion with evidence of
HBV infection
300–400 million with
chronic hepatitis B (CHB)
25–= 40% (75–160 million) die of cirrhosis or =
liv= er cancer
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Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0104.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
Hepatitis B Disease Progression
= Acut= e = Infe= ction
     Chronic&#= 13;
     Infection=
     Cirrhosis
Death
Torresi, J, Locar= nini, S. Gastroenterology. 2000.
Fattovich, G, Giustina, G, Schalm, SW, et al. Hepatology. 1995.  ;  Moyer, LA, Mast, EE. Am J Prev Med. 19= 94.
5%-10% develop HCC=
      Liver Failure
30% progress
 to Cirrhosis
=
Progression to
Chronic Infection
>90%  of chil= dren
<  5%  of adults
23% of Cirrhotic= s decompensate wit= hin 5 years
Liver
  Ca= ncer (HCC)
Liver Transplantation
(Decompensation)
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= Months
3D"Text
Cumulative Incidence Survival (%)
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
CP= H
CAH
Cir= rhosis
5 Year Survival in Chronic Hep= atitis B
=
=
Weis= sberg, JI, et al. Ann Intern Med. 1984;101:613-616.
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Hepatitis B and= Risk of HCC
Yang, HI, et al.= N Engl J Med. 2002;347:168-174.
= 12
= 10
= 8
= 6
= 4
= 2
0
3D"Text=
Cumulative Incidence of HCC (%)
0 1 2 3 4 = 5 6 7 = 8 9 10
Year<= /div>
HBs= Ag+, HBeAg+
HBsAg= +, HBeAg-
HBsAg-, HBeAg-
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1.00
0.96
0.92
0.88
0.84
0.80
0
1
2
3
4
5
6
7
8
9
10
11
12
Survival Distribution Func= tion
Survival Time (Years)
HBV = DNA Low (+)
1.6x103– <10= 5
RR= =3D1.5 (0.2–11.8)
HBV = DNA (-)
HBV = DNA High (+)
>105
RR= =3D13.4 (1.9–97.1)
Chen G = et al 55th = AASLD Boston MA Nov 2004; Poster 1362
Chronic Liver Disease Mortality by <= /span>HBV Viral Load at Baseline
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Survival Distribution Function
Survival T= ime (Years)
HBV DNA High (+)
>105
RR=3D9.9 (3.231.0)
HBV DNA Low (+)
1.6x103– <10= 5
RR=3D1.8 (0.5–5.8)
HBV DNA (-)
Chen G = et al 55th = AASLD Boston MA Nov 2004; Poster 1362
HCC Mortality by HBV Viral Load
at = Baseline
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Active-passive Hepatitis B immunization
<= /span>prevention is the best way to cont= rol hepatitis B
<= /span>active-passive immunization succes= sful in 95 % of the children
= hepatitis B immunization is a canc= er vaccine in reducing the incidence of HCC to 1/4-1/3 of that in children born before the hepati= tis B vaccination era in Taiwan
= pregnant women must be checked for= HBV = markers
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0107.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
Goals of Treatment
=
<= /span>Eliminate or significantly suppress H= BV replication
<= /span>Prevent progression of liver disease = to cirrhosis
and = liver failure
<= /span>Prevention of HCC <= /div>
<= /span>Improve survival
<= /span>Treatment endpoints
<= span style=3D'font-size:86%'>Nor= malize ALT
<= span style=3D'font-size:86%'>Dec= rease HBV DNA
<= span style=3D'font-size:86%'>Ind= uce HBeAg loss and seroconversion
<= span style=3D'font-size:86%'>Imp= rove histology
<= span style=3D'font-size:86%'>Pre= vent and/or reverse decompensation
Keeffe et al., Clinical Gastroenterology and Hepatology 2004; 2:87-106. 
Conjeevaram HS. J Hepatol. 2003;38:S90-S103<= /b>
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0120.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
Adapted from Liaw et al. N Engl J Med. 2004;351:1521-1531.
0
6
12
18
24
30
36
Disease Progression = = (% of patients)
Time (months)
Lamivudine
n=3D436
Placebo
n=3D215
0
5
10
15
20
25
P =3D 0.001
Effective Treatment May Slow
Dis= ease Progression
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AJA2AAAgbQAASBsAAJA2AAAgbQAASBsAAJA2AAAgbQAASBsAAJA2AAAgbQAASBsAAJA2AAAgbQAA SBsAAJA2AAAgbQAASBsAAJA2AACkDQAASBsAAJA2AACkDQAASBsAAJA2AACkDQAASBsAAJA2AACk DQAASBsAAJA2AACkDQAASBsAAJA2AACkDQAASBsAANIGAAAB8/9aVv11xxfmhwAAAABJRU5ErkJg gk== ------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0137.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
<= /span>
=
=
H= BeAg +ve
=
=
H= BeAg –ve /
a= nti-HBe +ve
Natural Course of Chronic HBV Infection
=
=
P= hases of H= BV infection
=
=
Replicative or immune tolerance phase
=
=
HBeAg
clearance
=
=
Low-replicative phase
HBV reactivation
=
=
Wild-type HBV
=
=
Variant HBV
Brunetto J H= epatol 1991
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Acute hepatitis B
è usually not indicated
Inact= ive carrier
è not indicated (except in case of prophy= laxis of reactivation before chemotherapy)
Chron= ic hepatitis B, HBeAg+
è if HBV DNA >105 and disease
Chron= ic hepatitis B, HBeAg-
è if HBV DNA >104 and disease
èKEEFFE et al, 2004
Treatment of hepatitis B: whom?=
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Recommendations for Treatment
Elevat= ed
> 104 copies/mL
Normal=            if disease
< 104 copies/mL
Normal=
Elevat= ed
> 105 copies/mL
Normal=            if disease
Keeffe Algorithm 2004
Yes
No
Yes
No
Yes
No
Yes
No
> 105 copies/mL > 2x ULN
< 105 copies/mL
N or &= lt; 2xULN
> 2= x ULN
> 105 copies/mL
N or <2xULN
EASL 2003
> 105 copies/mL
> 2= x ULN
Yes
No
< 105 copies/mL
<= ; 2 x ULN
HBeAg-
HBV DNA
ALT =
HBV DNA
ALT&= #13;
Yes
> 2= x ULN
> 105 copies/mL
<= ; 2x ULN
HBeAg +&= #13;
HBV DNA&= #13;
ALT
AASLD 2004
* Keeffe et al. Clinical Gastroenterology and Hepatology, 2004; 2:87-106
*
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Current Treatment Options
Adapted from Lok ASF= . HBV Treatment Guidelines: Questions and Controversies
EASL Consensus Conference,  J Hepatol, 2003
= Injection
= Side effects frequently reported
<= /span>Finite duration of treatment <= /b>
= Durable post-treatment = response
= No report of resistant = mutations
Interf= eron
= Long /indefinite therapy <= /span>
= Moderate viral load reduction
= Oral
= Effective against wild-type and LVD resistant HBV
= Low rate of resistance<= /span>
Adefov= ir
= Long /indefinite therapy =
= Significant rate of resistance with long term therapy
= Oral
= Negligible side effects=
Lamivu= dine
Weaknesses=
Strengths<= /div>
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Integrated Resistance Surveillance Across ADV Studies (0-144 weeks)
Incidence of ADV Compared to Lamivudine Resistance
=
=
=
= Delayed and infrequent emergence of a= defovir = resistance mutations
1. Lai et al Clinical Infectio= us Diseases (2003) 36:687
2. Westland et al. Hepatology = July 2003
0%
24%<= /b>
2.0%=
42%<= /b>
3.9%=
53%<= /b>
70%<= /b>
0%
10%
20%
30%
40%
50%
60%
70%
80%
year 1<= /span>
year 2<= /span>
year 3<= /span>
year 4<= /span>
Incidence of Resistance
LAM1 (YMDD)
ADV (N236T+A181V)2
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Long-Term Data on Treatment With Adefovir in HBeAg-Negative Patient= s
Cumulative genotypic resistance by Year 5, 28.6%
4 (3%) by Yr 5 had increase in creatinine of ≥ 0.5 mg/dL=
Hadziyannis et al. = AASLD 2005. Abstract LB14.
0 <= /div>
3 <= /div>
11 <= /div>
18 <= /div>
28.6
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100
Year<= /div>
1
2
3
4
5 3D"Text
Cumulative =
Genotypic Resist= ance, %
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Long-Term Data on Treatment With Adefovir in HBeAg-Negative Patient= s
> 5% of patients had HBsAg loss by Year 5
50% had regression of <= span style=3D'position:absolute;top:47.0%;left:55.61%;width:36.14%;height:5.25%= '>bridging fibrosis or cirrhosis by Year 5
1-point reduction in Ishak fibrosis score =
Year 4 cohort, 55%
Year 5 cohort, 71%
Hadziyannis et al. = AASLD 2005. Abstract LB14.
65 <= /div>
70 <= /div>
67 <= /div>
69 <= /div>
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100
HBV DNA
< 3 log10=  copies/mL=
Normalized ALT
Yr 4 cohort
Yr 5 cohort
n
30
55
40
55
3D"Text
Pa= tients, %
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ETV-022: HBeAg-Positive Patients Treated Up to 96 Wks With Entecavi= r
Gish et al. AASLD 2= 005. Abstract 181.
= Cumulative Outcome by Week 96
3D"Text
Pa= tients %
Ente= cavir (n =3D 354)
Lami= vudine (n =3D 355)
80 <= /div>
39 <= /div>
31 <= /div>
26 <= /div>
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100
HBeAg
Seroconversion
Undetectable =
HBV DNA*
P < .0001<= /span>
= Sustained Responses 24 Weeks Off Therapy
31 <= /div>
71 <= /div>
29 <= /div>
69 <= /div>
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100
Ente= cavir (n =3D 111)
Lami= vudine (n =3D 93)
HBeAg
Seroconversion
Undetectable =
HBV DNA*
*Undetectable HB= V DNA, < 300 copies/mL
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file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0142.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
ETV-022: HBeAg-Positive Patients Treated Up to 96 Wks With Entecavi= r
Gish et al. AASLD 2= 005. Abstract 181.
= Cumulative Outcome by Week 96
3D"Text
Pa= tients %
Ente= cavir (n =3D 354)
Lami= vudine (n =3D 355)
80 <= /div>
39 <= /div>
31 <= /div>
26 <= /div>
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100
HBeAg
Seroconversion
Undetectable =
HBV DNA*
P < .0001<= /span>
= Sustained Responses 24 Weeks Off Therapy
31 <= /div>
71 <= /div>
29 <= /div>
69 <= /div>
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100
Ente= cavir (n =3D 111)
Lami= vudine (n =3D 93)
HBeAg
Seroconversion
Undetectable =
HBV DNA*
*Undetectable HB= V DNA, < 300 copies/mL
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0142_image011.png Content-Transfer-Encoding: base64 Content-Type: image/png iVBORw0KGgoAAAANSUhEUgAAABYAAABYAQMAAADLKJVkAAAAAXNSR0ICQMB9xQAAAAZQTFRFAAAA ////pdmf3QAAAAF0Uk5TAEDm2GYAAAAJcEhZcwAACDYAAAg0Ab6QHjwAAAAZdEVYdFNvZnR3YXJl AE1pY3Jvc29mdCBPZmZpY2V/7TVxAAAAeElEQVQoz2NgoBTUALELAwMfkGZsALILGBj4exgYOIBs /gY8+mYA1e8BYhMgTgHiN0CxE0CahYGB/Q8DA/MPIBumFshn/APlN0DZf5DMegHRz6gCxSC5Hwhp 3j8QDAJ4zXeBusUG4j4YYAf55QDQTw4IzP8HggkAANjUHfCezAM5AAAAAElFTkSuQmCC ------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0144.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
Nucleoside/Nucleotide Analogues
Comp= ound
Comp= any
Stat= us
Acti= vity
Lami= vudine
GlaxoSm= ithKline
Approve= d for HBV 1998
HIV, HB= V
Adef= ovir
Gilead<= /span>
Approved for HBV 2002 US
2003 Europe
HIV, HB= V
Telb= ivudine
Idenix/= Novartis
In deve= lopment for HBV
HBV onl= y
Emtr= icitabine
Gilead<= /span>
Approved for HIV
In development for HBV
HIV, HB= V
Ente= cavir
Bristol= -Myers Squibb
Approved 2005 US = 3;
Not currently approv= ed
elsewhere in the wor= ld
HBV onl= y
Teno= fovir
Gilead =
Approved for HIV
In development for HBV
HIV; HB= V
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0080.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
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quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
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CUUtFAH/2Q== ------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0079.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
=
=
Peginterferon alfa-2a (= 40KD) (PEGASYS®) monotherapy is more effective than &= #13;
lamivudine monotherapy in the treatm= ent of
HBeAg-negative chronic hepatitis B&#= 13;
72-week results from a Phase III, par= tially double-blind study
P Marcellin, GKK Lau, F Bonino, P Farci, S Hadziyannis, =
R Jin, Z-M Lu, T Piratvisuth, G Germanidis, N Pluc= k
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lamivudine 100 mg qd
PEGASYS® 180 = mg qw + lamivudine 100 mg qd
PEGASYS® 180 = mg qw + oral placebo qd
0
24
48
24 week
follow-up
72
Study weeks
=
<= span lang=3DEN-US style=3D'font-family:"Angsana New";mso-ascii-font-family:Aria= l; mso-fareast-font-family:"Angsana New";mso-bidi-font-family:"Angsana New"; mso-hansi-font-family:"Times New Roman";color:white;mso-special-format:las= tCR; display:none'>
Randomised
EOT
48 w= eeks
EOFU
72 w= eeks
<= b>Patients with HBeAg-negative CHB were randomised using a 1:1:1 rati= o
ITT population: n= =3D537
Study Design
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Key Inclusion Criteria
HBsAg positiv= e for ³6 months
HBeAg negative, anti-HBe positive for ³6 months
HBV DNA >100,000 cp/mL
- (COBAS AMPLICOR HBV MONITOR®<= /b>)
Serum = ALT >1 but £10 x ULN at screening
Less t= han 20% with serum ALT 1–2 x ULN
Liver = biopsy proven CHB
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Study Endpoints
= Co-primary endpoints
= Normal ALT (£1 x ULN) at end of follow-up <= /b>
= HBV DNA <20,000 cp/mL at end of follow-up
(COBAS AMPLICOR HBV MONITOR<= /b>®<= /b>)
= Secondary endpoints
= HBV DNA over time <= /span>
= Histology at end of follow-up (Ish= ak)
= HBsAg loss/seroconversion at end of follow-up
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59%
44%
3D"Text
Patients (%)
PEGA= SYS® 
+ pl= acebo
PEGA= SYS® 
+ la= mivudine
lamivudine
60%
n=3D177
n=3D179
n=3D181
P=3D0.915
P=3D0.003
P=3D0.004
Normal ALT at
End of Follow-up (Week 72)
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3D"Text
Patients (%)
n=3D177
n=3D179
n=3D181
43%
29%
44%
P=3D0.849
P=3D0.003
P=3D0.007
PEGA= SYS® 
+ pl= acebo
PEGA= SYS® 
+ la= mivudine
lamivudine
HBV DNA <20,000 cp/mL at
End of Follow-up (Week 72)
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0
10
20
30
40
50
60
30
20
10
3D"Text
Patients (%)&#= 13;
= 56%
= 11%
= 16%
= 46%
= 46%
= 17%
lamivudine
PEGASYS® + placebo
PEGASYS® + lamivudine
Improvement
≥2 point reduction
 in score
Worsening
≥2 point increase
 in score
Necroinflammatory Activity at End of Follow-up (Week 72): Patients with Paired Biops= y
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P= =3D0.030
P=3D0.007
P=3D0.029
0 (0%)
5 (3%)
7 (4%)
HBsAg loss,  n (%)
lamivudine
(n=3D181)
PEGASYS®
+ lamivudine
(n=3D179)
PEGASYS® 
+ placebo
(n=3D177)
0 (0%)
3 (2%)
5 (3%)
‘s’ seroconversion,  n (%)
HBsAg Loss and Seroconversion at <= br> End of Follow-up (Week 72)
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Treatment of hepatitis = B: conclusions = ;
<= span style=3D'font-family:"Arial Unicode MS";font-size:88%;color:blue;mso-color= -index: 0;visibility:hidden'>
Many hepatitis B patients will progress <= span style=3D'position:absolute;top:32.0%;left:8.42%;width:85.95%;height:7.25%'= >spontaneously to inactive carriership Current therapy aims at accelerating the natural history of HBV infection towards progression to = inactive carriership The efficacy of current regimens depends on the = competence of the host adaptive immune response to HBV antigens
<= span style=3D'font-family:"Arial Unicode MS";font-size:88%;color:blue;mso-color= -index: 0'>Seroconversion to anti-HBs is still very rare
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=
=
P= ersistent HCV infection
=
=
A= cute HCV infection
=
=
Liver cirrhosis<= /span>
=
=
Liver failure =
=
=
S= ymptomatic
=
=
A= symptomatic
=
=
F= LF
=
=
&l= t;0.1%
=
=
~20%
=
=
Prob. 100%
=
=
~80%
=
=
80%
=
=
~50%
=
=
2-2= 0% over 20 years
(disease modifie= rs)
=
=
C= hronic hepatitis C
=
=
Primary liver cancer =
=
=
2-5% per year
=
=
2-4% per year
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HCV and extrahepatic manifestations
glomerulonephritis=
fibromyalgia
lichen planus
diabetes
CNS vasculitis
skin vasculitis
PCT
non-Hodgkin B lymp= homa
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Treatment of Chronic Hepatitis C=
PE= G-Interferon-a + ribavirine is superior to <= span style=3D'position:absolute;top:31.25%;left:8.98%;width:103.37%;height:6.5%= '>standard IFN-a combination or (PEG)-I= FN-a alone
Pa= tients with genotype 1: PEG-IFN-a<= /span> + ribavirine for 48 weeks
 » 51% SVR rate
Pa= tients with genotypes 2 and 3: PEG-IFN-a + ri= bavirine for 24 weeks
 » 80 % SVR rate
NIH Consensus on Hepatitis C, 2002
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PegIntron + Rebetol
Sust= ained Virologic Response - All Genotypes
47%
47%
54%
0%
20%
40%
60%
80%
3MIU + Riba
Peg 0.5 mg/kg
+ Riba
Peg 1.5 mg/kg
+ Riba
*
*
Peg 1.5/800  = vs. I/R p=3D0.01
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PegIntron + Rebetol
Sus= tained Virologic Response - Genotype 1
33%
34%
42%
0%
10%
20%
30%
40%
50%
3MIU + Riba
Peg = 0.5 mg/kg
+ Riba
Peg 1.5 mg/kg
+ Riba
*
Peg 1.5/800  vs. I/R p=3D0.02
*
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PegIntron + Rebetol
Sustained Virolog= ic Response - Genotype 2/3<= /span>
79%
80%
82%
0%
20%
40%
60%
80%
100%
3MIU + Riba
Peg 0.5 mg/kg
+ Riba
Peg 1.5 mg/kg
+ Riba
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0
10
20
30
40
50
60
70
80
90
84
81
79
80
= n=3D96
= n=3D144
= n=3D99
= n=3D153
3D"Text
SVR (%)
PEGASYS® (40KD) 180 mg qw=
PEGASYS® (40KD) Pl= us COPEGUS®:
SVR = in Patients With HCV Genotype 2 or 3 (ITT Analysis)*
= 24 Weeks
= 48 Weeks
Hadziyannis et al. Ann Intern Med. 2004.
COPEGUS® 
800 mg/day
COPEGUS® 
1000/1200 mg/day
COPEGUS® 
800 mg/day
COPEGUS® 
1000/1200 mg/day
*Intent= -to-treat analysis.
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0017_image024.png Content-Transfer-Encoding: base64 Content-Type: image/png iVBORw0KGgoAAAANSUhEUgAAABcAAABUAQMAAABTKD4hAAAAAXNSR0ICQMB9xQAAAAZQTFRFAAAA ////pdmf3QAAAAF0Uk5TAEDm2GYAAAAJcEhZcwAACDYAAAg0Ab6QHjwAAAAZdEVYdFNvZnR3YXJl AE1pY3Jvc29mdCBPZmZpY2V/7TVxAAAAoElEQVQoz41QMQ7CMBAzypAO1d3KBN9ga5+ExMKA1Gx8 q114B1tHGBmQgh1aVQwgTrISX+zzKcA/lRNivsPzA4bd0o8J8B6oWlSE8R7PCasr347EBoX70FPS SlbksqkM6zJTs5XxvRLCwB1GzrolWEfviWCG7d9w+mfUdLhW4x7hSdKRbIkwneTq6126ekoJ2rdh r2HG4RM+Kp+ay8+fegFQ2jKh6xEeDAAAAABJRU5ErkJggk== ------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0014.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
PEGASYS® (40KD) Pl= us COPEGUS®:
SVR = in Patients With HCV Genotype 1 and Low Viral Load*
0
10
20
30
40
50
60
70
41
52
55
65
= n=3D51
= n=3D71
= n=3D60
= n=3D85
3D"Text
SVR (%)
= 24 Weeks
= 48 Weeks
COPEGUS® 
800 mg/day
COPEGUS® 
1000/1200 mg/day
COPEGUS® 
800 mg/day
COPEGUS® 
1000/1200 mg/day
PEGASYS® (40KD) 180 <= /b>mg qw=
Hadziyannis et al. Ann Intern Med. 2004.
*Intent= -to-treat analysis.
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0014_image025.png Content-Transfer-Encoding: base64 Content-Type: image/png iVBORw0KGgoAAAANSUhEUgAAABcAAABUAQMAAABTKD4hAAAAAXNSR0ICQMB9xQAAAAZQTFRFAAAA ////pdmf3QAAAAF0Uk5TAEDm2GYAAAAJcEhZcwAACDYAAAg0Ab6QHjwAAAAZdEVYdFNvZnR3YXJl AE1pY3Jvc29mdCBPZmZpY2V/7TVxAAAAnUlEQVQoz4VQQQrCMBCcJaV7EfoBD32Gglh/Zn/gE/qV gB8J+AGhBz2I6UwICoJ0YUhmMzuzBFirc0TIT3h+wbH99kMEPAFNj4Zw3sOVvTvfDkSHwj0lSnrJ ilxjKsemeMpbGf/rBEvcYabXgxhG+JHzzPBdRY4ftPLWatzD3iQDSUdYPcnV17t0bU2xC3eb6D3R Z/+DWfkj7Lb6WwuhITcz2HrBCAAAAABJRU5ErkJggk== ------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0015.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
0
10
20
30
40
50
16
26
36
47
n=3D50
n=3D47
n=3D190
n=3D186
PEGASYS® (40KD) Pl= us COPEGUS®:
SVR in Patients Wi= th HCV Genotype 1 and High Viral Load*
3D"Text
SVR (%)
= 24 Weeks
= 48 Weeks
COPEGUS® 
800 mg/day
COPEGUS® 
1000/1200 mg/day
COPEGUS® 
800 mg/day
COPEGUS® 
1000/1200 mg/day
PEGASYS® (40KD) 180 <= /b>mg qw=
Hadziyannis et al. Ann Intern Med. 2004.
*Intent= -to-treat analysis.
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3D"Text
SVR (%)
19%
Peginterferon Alfa-2b (12KD) Plus RBV:
SVR in HCV Genotype 1 Low Viral Load
IFN a-2b + R= BV
PEG-IFN -2b (12= KD) 1.5 mg/kg + RBV<= /b>
Percent of Study = Popu= lation
68
43
0
10
20
30
40
50
60
70
80
PEG-Intron™. PDR  ®. 56th ed. 2002.
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3D"Text
SVR (%)
50%
Peginterferon Alfa-2b (12KD) Plus RBV:
SVR in HCV Genotype 1 High Viral Load
IFN a-2b + R= BV
PEG-IFN -2b (12= KD) 1.5 mg/kg + RBV<= /b>
Percent of Study = Popu= lation
30
29
0
10
20
30
40
50
60
70
80
PEG-Intron™. PDR  ®. 56th ed. 2002.
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3D"Text
SVR (%)
29%
Peginterferon Alfa-2b (12KD) Plus RBV:
SVR in HCV Genotype 2/3
IFN a-2b + R= BV
PEG-IFN -2b (12= KD) 1.5 mg/kg + RBV<= /b>
Percent of Study = Popu= lation
82
79
0
10
20
30
40
50
60
70
80
PEG-Intron™. PDR  ®. 56th ed. 2002.
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Treating Patien= ts with
Chronic Hepatitis C: Whom?
Consider patient’s wish, contraindications
Monitor patients with F0 - F1 (irrespectively of the A score), <= /span>= due to the low risk of progression of liver disease in the absence of cofactors
Consider treatment of F0 – F1 only if:
patient presents with extra-hepatic manifestation (e.g. <= span style=3D'position:absolute;top:61.25%;left:11.42%;width:85.58%;height:5.5%= '>vasculitis due to cryoglobulinemia)
patient is highly motivated and wishes to become virus fr= ee
Treat if the fibrosis score is ³ F2 (irrespectively of the A sc= ore)
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Factors affecting fibrogenesis and response to therapy in HCV infection
Ye= s
Ye= s
Steatosis
Ye= s
Ye= s
Insulin resistance
Ye= s
Ye= s
Overweight
Un= clear
Ye= s
HBV coinfection<= span style=3D'font-family:Tahoma;font-size:79%;color:blue;mso-color-index:0; mso-special-format:lastCR;display:none'>
Ye= s
Ye= s
HIV coinfection
Ye= s
Ye= s
Alcohol abuse
Ye= s
No=
Viral load
Ye= s
Un= clear
Genotype
Ye= s
Ye= s
Sex
Ye= s
Ye= s
Age
Affects treatment response
Affects fibrogenes= is
Factor
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0087.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
Final Week-72 Results of APRICOT:
A Randomized, Part= ially Blinded,
International Comp= arative Trial of Peginterferon alfa-2a (40 kDa)
(PEGA= SYS®) ± Ribavirin (COPEGUS®)
vs Interferon alfa= -2a + Ribavirin in the Treatment of HCV in HIV-HCV Co-infection
Francesca J. Torr= iani M.D.
University of Cal= ifornia, San Diego
------=_NextPart_01C648DB.ABF02E80 Content-Location: file:///C:/D009C636/Hepatitis_reproductive_health_Male_2006_files/slide0088.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Viral hepatitis in reproductive health - Pierre Jean Malè
AIDS
PEGASYS®<= b>
Ribavirin
International
CO-Infection
Trial
HIV-HCV Co-infect= ion Study
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