HBV Factors and Clinical Outcomes M Omata
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![Page 1: HBV Factors and Clinical Outcomes M Omata](https://reader037.fdocuments.us/reader037/viewer/2022110101/56812baa550346895d8fda0b/html5/thumbnails/1.jpg)
HBV Factors
and
Clinical Outcomes
M Omata
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Genotypes
in China and Japan
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Miyakawa Y et al. Intervirology 2003
North East AsiaWest Asia
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North East Asia
West Asia
B and C
D
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Any Difference Between B and C
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HBeAg-positive
Years
Born Infected ALT
Natural CourseHBV Infection
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As with Flares
Years
eAg Seroconversion
ALT
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HBeAg Seroconversion
When Induced Naturally?
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This Timing of Seroconversion Varies
Any Differences among
Genotypes ?
HBV
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Genotypes & Seroconversion
BJ McMahon
1158 Eskimos for 20.5 years
GASTROENTEROLOGY 2007
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SE Livingston Gastroenterology 2007 in press
Genotype No. of patients
Age at time of HBeAg
clearance
A 34 19B 6 20C 36 48D 305 18F 126 16
Clearance of HBeAg in Alaskan natives
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Genotype C is
Late Seroconverter
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Relation to Liver Diseases
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Yang HI, J Natl Cancer Inst 2008
Genotype and HCC
Genotype B
Genotype C
39/803 (4.9%)
40/358 (11.1%)
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Age of HCC and Genotypes
20’s 30’s 40’s 50’s
Orito et al. Hepatology 2001
60’s >60
No. of Pt.
40
20
B
C
B
C
n=117
Ages
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The longer period of
eAg-pos/high viral loadMay
Bring more PatietnsTo HCC
Genotype C
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Interferon Effect and Genotypes
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e Loss & Seroconversion
37%
51% 49%55%
60% 60%
40%
52% 52%58%
67% 69%
0
20
40
60
80
0 1 2 3 4 5
HBeAg seroconversion HBeAg loss
Perc
ent
Wong VW, et al. Hepatology. 2010;51:1945-1953
Yrs Post-Peg IFN
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32%
14%
B C
HBeAg Clearance
Genotype & HBeAg Clearance
13/41
9/66
Interferon Therapy
Wai CT, Hepatology 2002Genotype B Genotype C
32%
14%
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Buster EH, Gastroenterology. 2008
Interferon & HBsAg Clearance
Follow-up 3 years
0
10
20
30
40
50
60
70
80
Pro
port
ion
of i
niti
al r
esp
on
ders
(%)
Genotype C (n=9)Genotype B (n=7)
14%
HBsAg negative
0%
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Response to PEG-IFN in HBeAg positive CHB
HBeAg Loss HBsAg Loss 2
1 Janssen, Lancet 2005; 2 Flink, Am J Gastro 2006
0
10
20
30
40
50
A n=90
28%
47%44%
25%
Bn=23
C n=39
D n=103
Per
cen
tag
e o
f p
atie
nts
(%
)
0
3
6
9
12
15
A n=90
3%
9%
2%
Bn=23
C n=39
D n=103
1814%
Per
cen
tag
e o
f p
atie
nts
(%
)
1
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How About
Response
To Nucs ?
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Nuc and Genotype
Kobayashi M, J Med Virol. 2006
0
20
40
60
80
100
0 24 48 96 144 >192
Weeks
HB
V D
NA
Cle
ared
(%)
84%
76%
47%
Genotype C (449)
Genotype B (38)
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How about Human Genotype ?
Host Factors
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IL28B in HBV infection ?
In hepatitis C, Strong AssociationIL28B gene and Response to PEG-IFN + RBV
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IL28B Genotype Distribution
p<0.001
AA
AG GG
AA (and CC) predominates in
Asians
Sonneveld et al. Gastroenterology 2012 in press
AA
AG
GG
Asians (n=133)
Non-Asians (n=133)
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Factors
Viral
Human
Genotypes
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Adjusted for HBV genotype and baseline ALT and HBV DNA
33628824019214496480
80
60
40
20
0
AA
AG/GG
P=0.018
HB
eAg
Ser
oco
nve
rsio
n (
%)
weeks
IL28B PEG-IFN induced HBeAg & HBsAg Response
Sonneveld et al. Gastroenterology 2012
AG/GG
AA
P=0.042
33628824019214496480
10
8
6
4
2
0HB
sAg
Ser
ocl
eara
nce
(%
)
weeks
N=205
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We, Asian, may have been infected by Tougher Virus,
but may haveFavorable Genotype for Treatment
But this is yet to be proven in larger Asian population
And including more SNPs
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Interacting “Genotypes” may answer
many of un-answered questionsIn HBV infection
Studies for the Future
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Nature Review GastroHepatol 2012;9:69-70
a big step forward
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Nature Review GastroHepatol 2012;9:69-70
a big step forward
GWAS
Whole Genome Sequencing
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Ion Proton
You can get 3 billionIn a day
3 billion AGCT
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1979 2012
3000nt 3000000000nt
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Central/Kita Hospitals
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Greatly appreciate your patience
謝謝
Prof Q Ning
and
Staff
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劇症肝炎 Pre-core Mutant
Omata M N Engl J Med 1991;324:1699-1704
Pre-core Mutant
7/9 Fulminant
0/10 Acute
Immediate Suppression of Virus Replication Badly Needed
6 4歳女性Omata K
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NanoPore
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