HBV Factors

and

Clinical Outcomes

M Omata

Genotypes

in China and Japan

Miyakawa Y et al. Intervirology 2003

North East AsiaWest Asia

North East Asia

West Asia

B and C

D

Any Difference Between B and C

HBeAg-positive

Years

Born Infected ALT

Natural CourseHBV Infection

As with Flares

Years

eAg Seroconversion

ALT

HBeAg Seroconversion

When Induced Naturally?

This Timing of Seroconversion Varies

Any Differences among

Genotypes ?

HBV

Genotypes & Seroconversion

BJ McMahon

1158 Eskimos for 20.5 years

GASTROENTEROLOGY 2007

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

Genotype C is

Late Seroconverter

Relation to Liver Diseases

Yang HI, J Natl Cancer Inst 2008

Genotype and HCC

Genotype B

Genotype C

39/803 (4.9%)

40/358 (11.1%)

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

The longer period of

eAg-pos/high viral loadMay

Bring more PatietnsTo HCC

Genotype C

Interferon Effect and Genotypes

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

32%

14%

B C

HBeAg Clearance

Genotype & HBeAg Clearance

13/41

9/66

Interferon Therapy

Wai CT, Hepatology 2002Genotype B Genotype C

32%

14%

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%

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

How About

Response

To Nucs ?

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)

How about Human Genotype ?

Host Factors

IL28B in HBV infection ?

In hepatitis C, Strong AssociationIL28B gene and Response to PEG-IFN + RBV

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)

Factors

Viral

Human

Genotypes

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

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

Interacting “Genotypes” may answer

many of un-answered questionsIn HBV infection

Studies for the Future

Nature Review GastroHepatol 2012;9:69-70

a big step forward

Nature Review GastroHepatol 2012;9:69-70

a big step forward

GWAS

Whole Genome Sequencing

Ion Proton

You can get 3 billionIn a day

3 billion AGCT

1979 2012

3000nt 3000000000nt

Central/Kita Hospitals

Greatly appreciate your patience

謝謝

Prof Q Ning

and

Staff

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

NanoPore