HBV DNA <400 copies/mL ALT normalization HBeAg loss

HBV
Frederik Nevens
Hepatologie
UZ Gasthuisberg KULeuven
WKBV september 2004
Prevalence of HBsAg Positivity in Europe
 0.2%
Very Low
0.3-1.0%
Low
1.1 - 5.0%
Intermediate
>5.0%
High
No data
I. Epidemiology in Belgium (1)
• Incidence Acute Hepatitis B*:
1982-84: 25/100.000 - year
1991-92: 6/100.000 - year
Age: 20 – 49 y
Sex: 73% males
* Devroey D et al.; Int. J. Infect. Dis. 1997
I. Epidemiology in Belgium (2)
Prevalence HBsAg+*
• Pregnant women: 0,67% (14-20%
HBeAg+)(1)
• Flanders (1993-1994): 0,7%(2)
• Cidex screening (2001): 0,4% (81/18.315)
*Development of chronic hepatitis B: 10%
(1) Tormans G et al. Soc Sci Med. 1993
(2) Beutels M et al. Eu J Epidemiol. 1997
II. Infectiology in Belgium
Mode of transmission*
• sexual activity
• travel endemic area: 27%
• IV drug abuse: 18%
→ Vaccination
* Van Damme P. et al., Arch. Public Health 1998
• Prof. Leroux-Roels
III. Natural History and Treatment of
Chronic Hepatitis B
Cirrhosis (F4)
Wie moet behandeld worden
= patiënten met risico op cirrose
→ Chronische hepatitis (=ALT↑)*
→ HBsAg + en ALT↑ en
HBV DNA > 20.000 IU/ml
* Risico op cirrose +/- 30% na 10 jaar
Wie moet niet behandeld worden
= HBsAg: +
ALT: nl
HBV DNA PCR - neg: blijvend risico op HCC?
- pos: kans op reactivatie*
→ risico op HCC
→ noodzaak tot follow-up
*Heropflakkering bij steroidwithdrawel cytostatica
Doel van de behandeling
= blijvende normalisatie ALT*
≠ eradicatie HBV (intrahepatisch ccc DNA)
Cfr. HBsAg- HBcAs+ lever
→20% reactivatie na OLT!
* Grootste kans indien HBeAg- HBeAs+ (seroconversie)
Welke behandeling
•
HBeAg+ 1) INFα: 5-10 MU 3/w sc 4-6m(1)
2) Lamivudine(2)(Zeffix®): 100 mg/dag
tot HBeAS+(30%)(kan jaren duren)
•
HBeAg- 1) Lamivudine
tot HBsAg- (10%)
2) INFα 1 – 1 ½ jaar.
(1)
(2)
Nucleoside analoog – DNA polymerase remmer
20% meer kans tot seroconversie met PEG INF
Resistensie op Lamivudine
• - > 50% na 5 jaar
- ↑ HBV DNA < 1 log
- ↑ ALT
Adefovir (nucleoside analoog): 10mg/dag
- bij cirrose overlap 3 maanden
- trager antiviraal effect
- resistensie na 3 jaar: enkele %
- aanpassen interval bij
nierfunctiebeperking
Actuarial Survival Post Transplant
Historical Comparison
100
Lamivudine (N=47)1
80
Long-term HBIg (N=209)2
60
Patients
surviving
(%) 40
No HBIg (N=67)2
20
0
1
2
Years
3
4
5
Perrillo et al., Hepatology 20011 and Samuel et al., N Engl J Med, 19932
Study 437 at 48 Weeks
Regression of Cirrhosis
50
45%
45
ADV 10 mg
40
35
30
Patients (%) 25
20
15
10
5
0
7%
PLB
3%
ADV 10 mg
Progression
(F3 to F4)
0%
PLB
Regression
(F4 to F3)
HBeAg clearance predicts
survival
Niederau C, N Engl J Med, 1996
Actuarial Survival in End Stage Liver Disease
Historical Comparisons
100
Lamivudine in decompensated CHB1
80
Patients
surviving
(%)
70%
60
55%
Cirrhosis2
40
20
Decompensated cirrhosis3
0
1
2
3
4
14%
5
Years
Perrillo et al., 20011, Weissberg et al., 19842, and De Jongh et al., 19923
Spontaneous HBeAg clearance
• Age at infection:
- Immune tolerant phase: 15% after 20 years
- Immune clearence phase: 70% after 10 years
• Higher rate of HBeAg clearence:
- older age
- elevated ALT
- female gender
- genotype B
McMahon, Ann Intern Med, 2001
Huang & Lok, Clin Liver Dis, 2003
Study 437
Efficacy through 72 Weeks: ALL ADV 10 mg*
78%
80
Week 24
Week 48
Week 72
67%
70
60
46%
50
44%
41%
Patients (%)
40
26%
30
20
23%
23%
14%
14%
13%
8%
10
0
HBV DNA
<400 copies/mL
ALT
normalization
*Kaplan-Meier estimates.
Marcellin, P, et al. Hepatology. 2002; Vol. 36, #840.
HBeAg loss
HBeAg
seroconversion
Addendum: Interpretatie HB serologie (1)
1.
2.
3.
4.
HBsAg- HBCAsHBCAsHBCAs+
HBCAs+
HBsAsHBsAs+
HBsAs+
HBsAs-
→
→
→
→
…
…
…
…
Addendum: Interpretatie HB serologie (2)
1. HBsAg+
2.
ALT nl
ALT↑
→
→
…
…