iamjemdlf1\^`&#,FY_;6Z[WG5 2! 9]cbkf<]L+
(MTSX-*0USXJ3QTSX* KTS'USRX7/AUS X)=VSX4PVSX
E7$ TSX7.USon"> @ GHI @pn N@D%
qnCO :?Bglhm G5 8glhm
       HBV.+,1E;7

*J.E=69CA(;>H3?
/0$#!"K(SNPs …

L43F;

HBs%-HBV DNA&/occult):5@<3B(82BHDI<I' 0BG
82' .+,1  …

HBV (M Zobein. Hepat Res Treat 2013)       

$("'#( de novo B ! &%         
De novo B" 17

Dde novo!E-98

B"DAHB!E19

7 #<.*#7DNA< .?C=B>CIon PGM<,2HBV7( 6)/;
AC@< .CLC Genomics Workbench69:minor
clone71%<5' 4.2%.!
37&<$10+       Bde novo B

Features







Acute hepatitis B (n=19)

de novo hepatitis B (n=17)

P Value

Male sex

11 (57.9)9 (50)

0.7380Age, years

40.18.0

58.05.3

0.0014

Peak ALT

2675.3648.7

801.5297.8<0.0001

Peak T-bill

13.04.5

13.97.6

0.8482

Peak PT%

50.614.4

64.115.1

0.2268Survival (n, %)12 (63.2)

12 (70.6)

0.3843

A=2, Bj=1, C=16

A=0,Bj=8, C=11<0.0001

C1653T

1/19 (5.3)

3/17 (17.6)

0.2379T1753C/G/A

3/19 (15.8)

5/17 (29.4)

0.1441

A1762T/G1764A

4/19 (21.1)

5/17 (29.4)

0.3297

G1896A

6/19 (31.6)

11/17 (64.7)

0.0012

G1899A

0/19 (0)11/17 (64.7)<0.0001

S3N

6/19 (31.6)

14/17 (82.3)

0.0022novel N-glycosylation in
the α-loop

1/19(5.3)

3/17(11.8)

0.238

Genotype
Mutations(core-promoter, precore)

Mutations (envelope)          

HBV"#$   !
de novo

AHB
600

600

500

500

400

400

300

300

200

200

100

100

0

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

:119

1 2 3 4 5 6 7 8 9 1011121314151617

:304
P=0.0193           

number of mutation sites
in the envelope region

AHB

de novo

250

250

200

200

150150100

100505000
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

:33

1 2 3 4 5 6 7 8 9 1011121314151617

:112
P=0.0069       

AHBde novo No.
12345678910111213
14
15
16
1718
19
20
21
2223
24
25
26
27
28
29
30
31
32
33
34
3536



etiology Genotype
nt1753
CAH
AH
C
C
AH
FH
C
AH
C
C
FH+(T>C:90.42%)
AH
CFH
CC
AH
AH
C+(T>C:91.26%)
AH
C
AH
C
Bj
FH+(T>C:83.26%)
AH
AeAe
AH
AH
C
AH
CC
AH
AH
C
De novo
Bj+(T>C:5.11%)
Bj
De novo+(T>C:4.07%)
De novo
Bj
De novoCC
De novo
De novo FHCC
De novo FH
De novoC
De novo
Bj
Bj
De novo
De novo FH
Bj
De novo FH
BjC
De novo+(T>G:84.94%)
De novoC
Bj
De novo+(T>G:3.11%)
De novoC
De novo
C+(T>C:49.25%,T>A:18.39%)

 

A1762T

G1764AG1896A

G1899A+(about100%)+(93.79%)+(about100%)+(about100%)+(1.19%)+(79.4%)+(about100%)+(about100%)+(about100%)+(about100%)+(about100%)+(93.59%)+(about100%)+(about100%)+(78.19%)+(about100%)+(about100%)+(about100%)+(about100%)+(84.76%)+(1.47%)+(98.50%)+(97.72%)+(97.85%)+(98.07%)+(97.67%)+(98.40%)+(97.30%)+(16.31%)+(23.48%)+(19.81%)+(1.08%)+(98.44%)+(97.42%)+(97.87%)+(89.11%)+(98.4%)+(14.02%)+(22.15%)+(19.46%)+(1.48%)+(98.11%)+(13.38%)+(9.13%)+(98.67%)+(98.27%)+(89.84%)       

G1896A 

Prevalent(%)

1005068.4%(13/19)

P = 0.0012

31.6%(6/19)
064.7%(11/17)35.3%(6/17)

denovonovo
acute
hepatitis Bdemutation(+)

 
Bhepatitis
de novode BnovoB mutation(-)

       

G1899A 

Prevalent(%)

10050100%(19/19)

P < 0.0001

64.7%(11/17)0%(0/19)035.3%(6/17)

de novode hepatitis
novo
acute
Bmutation(+)

BB
B
de novo
hepatitisde novomutation(-)

       

#" !$ "%&  

1899
G1899

U-G

(Ito K. Sakamoto K et al. J Gastroenterol 2017 review)               

M133T  

119 G

E

N

T
110

101

 I

SM 133

New glycosylation site

M
145
146

X

α- loopN

T

Immunodominantloop
N-X-S/T: N-glycosylation
site

101

163

ER lumen

ER membrane
Cytosol

Virion surface

III?

?
Virion interior(Ito K. et al. J Virol 2010)

Detected by Ultra deep sequencing
24.1%(7/29)

P<0.001

0%(0/64)       HBV

No.

Etiology

Genotype123456789101112131415161718192021222324252627282930313233343536

AH
AH
AH
FH
AH
FH
AH
FH
AH
AH
AH
AH
FH
AH
AH
AH
AH
AH
AH
De novo
De novo
De novo
De novo
De novo
De novo FH
De novo FH
De novo
De novo
De novo
De novo FH
De novo FH
De novo
De novo
De novo
De novo
De novo

CCCCCCCCC
CCCBj
Ae
AeCCCC
Bj
Bj
Bj
CCCCC
Bj
Bj
Bj
Bj
CC
Bj
CC



S3N substitution in theenvelope (99.16%)
(99.87%)








(98.22%)
 (97.97%)
 (98.93%)
 (99.13%)
 (76.8%)
 (70.0%) (19.72%)
 (98.88%)
 (98.08%)
 (98.92%)
 (98.09%)
 (82.34%)
 (15.93%)
 (97.46%)
 (99.09%)
 (99.00%)
 (98.11%)
 (98.61%)

novel N-glycosylation in
the α-loop

T123N (18.44%)

T115N (1.13%)

S131N+M133T (2.73%)

 (33.19%)
     G130N

N

Prevalent(%)

100

94.4%
(17/18)50

82.4%(14/17)

P=0.261
17.6%(3/17)

5.6%(1/18)
0de novo
de hepatitis
novo
acuteB mutation(+)

BB Bde novo
hepatitisde novo mutation(-)
       S3N

Prevalent(%)

100

50

68.4%
(13/19)P=0.0022

82.3%(14/17)31.6%(6/19)

17.6%(3/17)

0de novo
dehepatitis
novo
acute
B mutation(+)

BB
 Bde novo
hepatitisde novo mutation(-)
       

• De novo

AHB S3N, G1896A,G1899A                 