The Treatment of Hepatitis C - State of the Art - - Falk Aktuell

60 Pages·2008·1.7 MB·English

Falk Symposium 163, March 14 – 15, 2008, Hangzhou, China
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Discovery of HCV in 1989
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11 22
1. M. Houghton
2. Q-L Choo
3. G. Kuo
4. D. Bradley
Source: Nature Medicine 6, 1082 - 1086 (2000)
33 44
HEPATITIS C
• After infection 50 – 80 % develop chronicity
• Worldwide 170 Million chronic hepatitis C patients
• Main cause for hepatocellular carcinoma (HCC) +
liver transplantation in „the Western world“
• Incidence for HCC and liver cirrhosis increasing
HCV: 6 Major Genotypes
4
2c BEBE1 4a ED43
1
2a J6
2 1b J 1b A
1c G9
1a H77
1a HCV1
2b J8
5a SA13 5
G 93SE6165 A/E
HCV
AE 93TH253
A 85UGU455 A 9a VN004
A 94KEQ23
H BEVI997
H 10a JK049
H 90CF056
C 95IN2106
8a VN405
C 92BR025
C 86ETH222
B 83FRHXB2
C 6b Th580
3a NZL1
7a VN235
6a HK2
11a JK046 3b Tr 3
(10)
6
(7 8 9 11)
Diagnostics:
ultra sensitive PCR methods are requisite
Prognostic Threshold Sustained Viral Response
50 IU/ml
800,000 IU/ml 10 IU/ml
Roche
Roche Cobas HCV 2.0
Qual
TMA
Bayer Versant HCV 3.0
Qual
LCx HCV RNA Quantitative
CDx HCV RNA Quantitative
Roche Cobas TaqMan HCV
m2000 HCV RNA Quantitative
8 7 6 5 4 3 2 1
HCV RNA log IU/ml
Rationale to treat acute HCV infection
Chronic
10-50% 50-90%
Hepatitis C
Resolution
Early treatment
HEP-NET Acute HCV-I Study
24 weeks IFN alpha-2b monotherapy (first 4 weeks daily 5MU)
100%
98%
e
v 80%
i
t
a
g
therapy n=44
e
60%
n
natural course n=40

A
N
R 40% 30%
-
V
C
H 20%
Santantonio et al. (Bari, Italy)
0%
48
0 4 8 12 16 20 24
=F24
weeks
Jaeckel et al., NEJM 2001
HEP-NET Acute HCV-III Study
asymptomatische Patienten
Recruitment >95 patients
HEPATITIS C - Milestones
Discovery of HCV
(1989)
2008
First usage of
IFN alpha in
nonA, nonB
hepatitis
Chronic Hepatitis C:
Improvement by trial and error
Sustained virological response
80%
60%
40%
Optimization of dose and duration
20% IFN 48 weeks
IFN 24 weeks
0%
1988 1990 1992 1994 1996