醫學專欄~黃武雄-C型肝炎的重要進展

1. C
前言
C
( A B )
1989 Science
C
: C
RNA
C
: Cryoglobulinemia
( ) Membrano
-Proliferative Glomerulonephritis (MPGN,
)
C
:
C
!
C
C
C
C型肝炎的近年大事演進
1970 A

2. B 1975
Non-A, Non-B
(NANB hepatitis)
C
1989 QL Choo (
), G Kuo ( ), M Houghton, D
Bradley ( )
Science
NS4 5-1-1
Clone NANB hepatitis 92%
C C
!
1992 C
C
1986 case report
( )
NANB NEJM
(New England Journal of Medicine)
1993
ribavirin ( )
Sustained Viral response (SVR)
30%
(Gastroenterology)
2011 DAA(Direct
anti-viral agent) C
Boceprevir Telaprevir
Sustained
Viral response (SVR) 30%
Ib C SVR
80-90%
2013 DAA
:
2-3
DAAs
C 95-100%
SVR
C
病毒學及基因演化分析的進展
C
(Flaviriridae) 3500
(positive single
strand) RNA
C 9600 base pairs
3200 amino acid 10 ( )
400
(subtype) 200
C C
100 1a,1b C
(Hepatology)
:
( 30%

3. C型肝炎的病程及診斷進展
C
Anti - HCV EIA (Enzyme
Immunoassay) 3.0 HCV RNA
EIA 1-3.0
(A, B) EIAs
EIA (window
phase)
Anti-HCV EIA3.0
C
: C SVR
Anti-HCV titer
0.1 log C
(relapser) Anti-HCV titer
C型肝炎的免疫學進展
C
HCV NS5A
( ) 1 PKR P38
ISGs C
2 IL-8
Type 1 Receptor
2009 IL-28B
polymorphism HCV
/ Receptor (?)
DAAs HCV
1
C 2 Restoration
of intrinsic anti-viral defenses 3
receptor
Clearance of suppression on interferon
receptors
C型肝炎的治療進展
1996
2002
( )
SVR
30% ( C
SVR
< 1% !)
SVR C
70%
90%
; C
1/4 1/3
1/2
C
:
2007
STAT-C
(specifically targeted anti-viral therapy for

4. hepatitis C) DAA (Direct Acting
Agents) C
C DAAs
Boceprevir Telaprevir protease
inhibitors 2011
FDA
( )
Naïve Ib HCV 80-90% SVR
20-30 % DAAs
2013
95-100%
SVR12 ( 12
)
C
DAAs
C
90%
C 2016 10
Genotype
3 SVR12 SVR24
80% 2016 AAS
LD
DAAs
12 16 SVR12
90
總結
2015
C
30 50 C
2015
C DAA
60
C
2020
C
WHO 2016 C
2030
90% 65%
80%
C
--- C
C
2060
!

5. WSH
6 7
WSH

6. WSH
HCV Genotypes
Important relevant facts
7 main genotypes
Nucleotide diversity > 30%
Genotype 1 is most common (60 to 70 % of isolates) in the
USA and Europe; Genotypes 2 and 3 are less common in these
areas, while genotypes 4, 5, and 6 are rare:
Genotype 3 --in India, the Far East, and Australia
Genotype 4 --in Africa and the Middle East, Egypt
Genotype 5 -- in South Africa
Genotype 6 -- in Hong Kong, Southeast Asia
Genotype 7 -- in Central Africa
Most important determinant of response to treatment
Taiwan: 1b (50-60%), II a and II b
WSH
Natural history of chronic hepatitis C
70~80% 20~30%
30~40% 60~70%
Annual incidence of HCC
(/year )
0~1%
2~3%
2-7%
Acute hepatitis C
ResolvedChronic hepatitis
HCC
LCActive hepatitisInactive hepatitis
Abnormal ALTNormal ALT

7. WSH
WSH
Enzyme Immunoassays (EIAs) for the
Diagnosis of HCV Infection
Assay Sensitivity(%) Low-risk
Groups (%)
/ Normal LFT
High-risk
Groups (%)
/ Abnormal
LFT
Window
period
(WK)
EIA-1 70-80 30-50 70-85 15
EIA-2 90-95 50-60 90-95 9-10
EIA-3 95-98 25 - 7-8

8. 取 材 自 Polyak SJ, Khabar KS, Paschal DM, et al. Hepatitis C virus nonstructural 5A protein
induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response. J
Virol 2001; 75: 6095-6106.