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 .. Prof. Reza Malekzadeh,

.. Prof. Seyed Moayed Alavian,

.. Prof. Rahim Aghazadeh,

.. Prof. Anna SF Lok,

.. Prof. Mario Rizzetto,

.. Prof. Jens Rasenack,

.. Prof. William Carman,

.. Prof. Tarik Asselah,

.. Dr. Mehdi Mohammadnejad

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*".,... IU/ml)I~f'r' HBV DNA •
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CBC
real time PCRJ>,)"-!~'; quantitative HBV DNA •
HCV Ab, HDV Ab •
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IgG anti-HA V •
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(0,."...lS:.o..l.il.:>~,..::.),...,).»~~j'O'I •
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J> 'J ~ quantitative HBV DNA i.Sr.?0jl..l.i1 i.S~ i.S~jST ..:;;.3J )'4 4 •
i.S~ i.S~jST..:;;.3) ~4J.lc xL., p jllS"'))'! ,PCR
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HBeAb S HBeAg"::"""Ifj':i HBV 0-"j-o..:;...;~"-I~.::.}4,I.sI4.j)).::.
"::"""I;S:' 04.~ ·'::'''':'tS.r.$<>jl.l..i1 HBV ...,..,)':!S c.s"r' ~ 0lS:...1..:;:.;)"",).::.,
)~.sI4.j)).::.(qualitative HBV DNA PCR) ~ ..:;:.;)"'" "-I PCR i.r')r.
~l; .l..il':;~ 0,..} cr.11)':!j .'::').l..i ~j) HBV 0-"j-o":;"';~ "-I ~
01~ ..::.....,11"jl' ...l.Jb'::' Jly:.91 ..,.. 0-"j-o 4Y> }.~..: . 01)~ jll) HBV JWr.-C
real time PCR ,,;.S) "-Il~.ii .(quantitative HBV DNA) ...,..,)':!,..;s
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;;.s ...,..,y:>., 01~ 45 ..$i)"", ).::. . ...w-c.s" tS.r.$<>jl.l..ill) (r.. IU/ml J.::.lLo 4}i:i
(undetectable -tS.r.$/Ojl.l..i1 J,>l!r.-C 4.) ~ 0,..} ~...l..!.4}..I.ii.o cr. 1j1
..::. ,..:. c.s" ,,;.)j!
"-I~.I ~S~ jl IgG anti-HAV 01)~ tSlr. ..::.....,11"jl' .cr.1yi <>,~
w-S I, ~ anti-HA V tS l).::. 0 1} .•.-=! "-I S .::.,..:. I"~I A 4Y> ...,..sy:>.,
..:;...;~ "-I04.~ n· .::.,.l> 0'y:>.1).::. tSl.w~).::. ..::..::.yf ,jt)y.; A 4Y>.J...D
HIV #J>J""-O)'::'01)~.('j» . .l..i'::'¥-~ anti-HAY tSl)1.::. HBV 0-"j-o
..l..i"':' i.r')yir.;. ~ cr.1jl ~4
).::. <>;;.S"-I) HBV 0-"j-o":;"';~ "-I ~ 01)~ I"W "-I ~4.fiJ1 J ~ ~
...,..W J>J""-O)'::' 45 tS.::.I}II"W J.;.4 ~ . .::.,..:.~,:; (tSjsr--' 01)~
~L..} ..l..i.r.$)} tSP4~ ~ HBV ~ jI.l..iI<>.::.¥- ~ ~ 4 ~.::.;
~ .::.I}I ...::.....,1 HBsAb , HBsAg tS~L..} J.o~ HBV tSlr. tSP4~
.~ ..::..j4.).::. HBV.J...D w-S ls..l.o4 (~-HBsAb s HBsAg) """j)':!j "-I ~I

4 ..::.....,1 ~ '::'''':'I''~I r.;. anti-HBc ~L..} tSP4~ 0,..} 01~ "-I yfl
).::. .(isolated anti-HBc) .l..i)'::' ~ anti-HBc.b.Qj 45 (0":("':' ~I,.. tS.::.I}1
4...,..W ~ ~L...,~.::. tSlo~ ...::.....,I..,..:,ts' ~ ~L..} •.::.I}I cr. 1j1 tSl<>~
.::.~, 0~.10J.;)'::' ...,..jy:>., ~~)~ C~"::"""I ~ 4. j .l..i)I.::.I) HBV
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~ IgM t~ jl anti-HBc '0..1..! 4i HBV V"s.r..s ~S)S 4s1 J>I)"')~ .s)~l.i
u-Sis 'y")jJ ~ ..::......1 ,,~ ,,~I~ 0L.!...i .~'-1 HBV 4i ~I ~),",~r" <\.iL.!...i
.sl}~ ~ ~ .s~I}1 ..l.....»~ A· l:i f::J. )~ HBsAb 0~ ~~,..., HBV........
u-S1j)-:i ~I}I ~14i..::......1 ~ ~1.r.L:.; !(\V)~~-.s""'~ ~anti-HBc
.~,..:. 'y")jJ HBV........
"L. n' l:i PyA J.91..l.» .sl")j~':"),.., 4i~'-1..)..l)I..)..l)} 0L.)~":;";":; ~ ";I;L~

ft.l HBV JWxi- ~l.i <? I.r..j •..)..l"':' ;st4j).s~ .s~;T ~ jI (}-1 ~
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...)..l~:J ~- HBeAg

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f~ ,,~I~ ~ j";),s' .:..~ ?)'" )~ ~ .sI.o...Jlb..o )~ .~'-1.s~ 4::>;;;
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Ji~u,""""Ij1~,..::.......1 \.,. •• IU/mlV"j;-tjH jJL.,}~";~ )~·uJ...?

'uJ...? u~.}T Ul")j~ u"'?"jI...I.j1 4 j ~I...I.j ul,,~ J...? ~~ I"'~I ~
),..J lx j S~ ),..J lx ~ jl h~ ..?J-I ....I.j~~lS" u~ I) U)~ ~
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.' • <.::t
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. ' \,J'•• ' . y
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0L.,)~ t,,"':" ~)jA )~ ti .J,.;...I1:,~lS" I"'~II) J...? ~~ j ..::.......1 ~ uJ...? ~....:,

Ul")j~ u"'?"jI...I.j1 I.; I) uj ·....:,4 01~ U)~ ~ ;!I .X..;S u.,,?~

'uJ...? ~}T~) ~4..::..)J-"»~ jx..;SlS"u~ HBV DNA jUJ...? u~}T
..J,.;...I1:,~lS"I"'~I~~
u'J-I45 JL.,}uJ...? ~}T4~ HBeAgul;l~ )~..:;.........I~0tlJ-l"j)l&;
~ HBeAg seroconversion JI»~ •..:;.........1 o~~I~ ~4 uJ...? u~}T)4 .:r-Jjl

~j~ r.""0L.,r-tif U)~~~)jA)~..:;.........I~."":'4~t>~~t>..:.J1>

HBeAg serocnversion 0 1.,w ,uJ...? u~}T 0J..o~..:r-t~ "::")J-"> )~ J jI

(')'~~I"'~")J...? ~~
J...? ~~~J-I)1S" ~~)jA4.j...l.j)...I.jJ...? ~~I"'~I~J,!W45~I)~)~
J...? jjr.e3 ~~# u~L.Z, •...I.j)~ ~~ ~~L.,} ul..bci4,
Jl!... 01~ ~ ·~4 ..l.;...o~r' 0L.,)~ t,r- ~)jA)~ u.,,?~ ulJ-l .x,j1,:;lS"

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.HBV DNA H jI ~ ~,...) •..I...!. ~~I DDRC ).:; cS (.$I.wl.h.).:;

.;.......;I~ ~HBeAg (.$1).:; oI)..,,,,:,:,!),:; jl1lA.....JLJ-llS:JT ,~';')I..o...:. '0=A,.~JT
c.r..~ o,;f).:; ./'\, )"!I)"! ROC ~)"i.j ~.;..j.:; 41) (.$~ ~~ JiL9 j,.r.::9
(n) . .l.S ~~ (validation group) ..::..i.,jl o,;f).:;·/ AO,
HBeAg (.$1).:; 0I)..o.,:,:,!)':; ~ \.S4~':; )"!)S .:;),... <l..:>:>G- )~ <I..i r , '(.$~
•..w:z,':;-.s"'0L!..i1)~ HBeAg,~

...:......1 0..>..1. 0~lA;:..,1 AO ~J"" jI J5:.:. 01. 1~ cSl",·

.(~,..:.~IJ""0"-""')~"':'.rr~1 HCC P jlcSJ~Jl.,.f jL,.;'::'J"" J~..I..

...:......1 o..>..1.o~lA;:..,IAO ~J"" jlJ5:.:. 01. 1~ cS l" ,*

.(~,..:.~IJ""0"-""')~"':'.rr~1 HCC pjlcSP4.f jL,.;'::'J"" J~..I..
 ~ ~~ ,.;~~ ul.oJ')
~ ~~ ~~ ~IoJ~ ~1~1
'"-1, ~)~ 0..l..! jl..,.,..::..;;~ .,..r,.r.., J.oIS ~~) ,C ..::..;;~ J)l.> )'I
r' '..,.,.;.riA"::";;~ 0L.)~ -s..4rJ J..l.Jl> ,~I ~r.J:. ~lr.j Jl.oz>.l
0~;S"",y
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UE'-.)'r.-')....,~;,;;)'IU·) .,..r,.r..,,,
A
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'"-1~;; 4·..:.......1 J,,9 J.oI~ jl ~li r."',S".. J.l'>1S ,}~,,~ ("~)IS jl

($l+lL..... ($1)'1 ($, ($~ ..l..:...ojl~ JI..l.Jl>I0t 1'"-1-s.~~ ($I)'I)~ -s.lr.j} ~ 1

,,x,r.?-s"}} "J:U ...... ~~ , ~;-9 s4r9..l.Jl> .~I';':J'"'"

0L.)~ ~I J..l.Jl> .~-HBeAg ti' jl .;.rro ..::..;;~ '"-1 ~ 01}.•.'<:o!)~
t"; jl.;.rro,,::,,;;~ '"-1 ~ w')~ 0L.)~)~ .~I HBeAg 0~ ~

'"-1.~I(",I ...... ),"",'"-1.,..r,.r-''''''Yr' ,ALT 0~JL.;J..l.Jl> .~-HBeAg

~.(~,),~)'!r .. • IU/mljlroS'"-1lr.,~~~ HBV DNAo!S ($;,"",

jI~ o...\.c )~JLO:iI0tI~}'1 !~IJlo~I)~'0L.)~S'))'I HBsAg0~

,..l.Jl>~-s"t;0IJ~

'"-1 j~ w')~ jl s)~ ...:.......1 ~..,.,.;.rro,,::,,;;~ 0L.)~ ~1 '"-1~;; 4

I.s:!')~'::'" ,li.o0~1~ t) Jl.oz>.l, ~':J4 ~,)~ ~ ,,x,)~":""",,';':J'"'" 0L.)~
0L.;~ ..l..:...oj~l,.jl, o!S ~~b,r.';I}....'<:o!)~~ 0L.)~..:.......1 ("j':J '~)~~¥?",,r.;
'($~ ($~;j Jlr.r'~' '0L.)~ t,,r. ~),...)~ ($r.?~ ($I)'I'~
,~r.?}}"J:U ...... ~4~ ...s:.r.)~~~, ')~\.r' .HBV DNA,;;.;;
($~0.r>-' I).;.rj-o ~..::..;;~ )~ ~ ...s:.r.)~~ ~cilr. ~~)~,,4

(",..,,,.. ~ .~)~ ~y:-, ~j 0t')~ ($~..u..... ~~0.r>-' ($~ . ..u.;$-s"

)'I o!S ~1 (Ishak scoring system) S~ 1~ ~~..bW jl ($)~' 01.r-')~
'"-1 (stage) ($~ j.!ld0 .r.--, (grade) ($~j,~ .!I..,.,~101.r.--'"-1wT .,..rL.....1
'
;.rl..l.>, \A )'11)'1 grade ;.rl..l.> ~ 0:: 1)" '"''':'I.S''' ""I" or" ~ISI~ ),Jo
~ 4. 'f t,)'II)'Igrade ,:./}:.oNIH olS}S~.rU ...,.,L...I)'I.('n).,.::.....M' )'11)'1 stage

.(11" ,I) ""':'l.S"'ci)' ~ )""",.rj-c..::...;;y,~..slA.}:-.... jl~,.:l,.~A.;

4. f j,~ stage .:}r.-o C .rj-c"::,,,;;y,)"..s.J.:S ~~ J..i19 ..s)~ S')L.l.oI

..r')'I.' r;; .'it,..s.J.:S ..s~;'i as ..s";-9 ..s)~ ~,,;;~ .(n) . ..:......1 ~
."),, (~4. f )'11)'1 stage)..s.J.:S ~~ J..i19 j,~, y.,. .. IVlmi jl J-.=;
..s.J.:S ~;T jI J~ ,.:"I~ A.; as ..s)~ '~)'I . ..:......10l.o)" .J..;..oj~,..s~
grade:f, Stage:'.J.:S ~~)",..:......I )")~)'I 0-='.4 ..r')'I.,r;;, Jl.o)
jI ..s)l::-i .Jl> 0::' t, .,,}~ j~ 0l.o)" A.; , ..:......1 ~ ..s)l.o.::I A.; ~ ."),,
(gray zone) 'it, J~ '" A.; ~ ~~ ~j~~ ..slA.ci4. 401)l.o.::I
, ...,.,')'1.' ~ ...s.J.:S ..s~;T J4.)""'~, .h,o.'~ 0:: 1)" '~I.S'" a.....::-IJ""
)YS..C ),JoA.; as ..s)l.o.::I..:......I~J~01~A.;."~)}~J..o~t,~)l.o.::I~
, Stage:\ ,Y',... IVlmi ..r,)'I.' ~ .Jl.o) )'11)'1'" j1 J-.=;..s.J.:S ..s~;1
0,~..sAaS.)l> )"!"A)}0l.o)"..:;..;.,J."),,.J.:S ~~)" grade: r
..s.J.:S ..s~;T t, .), .A.;L:.... ~J~~ ..slA.ci4. t, ~I~ )l.o.::I 0l.o)"
, 'it, ..s.J.:S ~;T ..sl}" 01)~ ...:......1 ~;I 0e!4 ..r')'I.' ~ , Jl.o"; ~
..s.J.:S ..s~;T ,y.S) 'it, Jic')'I.L... ~ jI ~t, ~ ~J~~ ..slA.ci4.
~1)l.o.::I~ ...J..i"':'..r))'I( ... ,D 4y, .j.s:JI.NASH .~,}"Jic'~l.o)

..slA.~l.!.laS <.Si)~ ),,04 )"..:......,~ ,..J..ir.? )}~"..sA..:;..;.,J ~4

('it, ..r')'I.'~ t,,,I~ 'i4)l::-i..s.J.:S ..s~;T)c...)..s.J.:S ..s)~.:;.J~
(rr).,,"':' ci)' yhi )"0l..:..,(' ..s')'I0l.o)" .",,}' rou;,~T)"
4. (ci~ ~j,~) 'f )'11)'1 stage, Jl.o;~..s.J.:S ~;T as ..s)~4J
\,: stage:'f ..sl}" 0')~ ,,),.. )" as ..s1.wU:..... )" ~ ..:......10l.o)" .J..;..oj~ ";i" ;;'it,
as ..l.!, ~ .~I" Jl.o";..s.J.:S ~;T dJ~ jlI.Y· 01)" '~r~1 ;;'iL;
},.t...>~y, r~)lS , o..L.!..)0 1r , j,r-'"" j,)'I ~l.o ..J..i1~1.S'" ..r')'I.'..;..Q 0l.o)"
."r.?;i}0l.o)"..:;..;.,J ..s)l.o.::I~..:......I~0::')'I~ Hrtl",..:.
y;Iy; HBV DNA j JLo'; ~ ..s~ ..s~y;1 ..sl).) ~ ..s)~ ..sly;
~ 's....O:;.!).) grade:\' j(~~j,~) stage: 'I" .}j,c....,I\·,··· IU/mi
,')).l.i')p'",~lS .wLb..j S)~..s)~~wLo).).))'Y').)~.);5' ..I.,(4~'.)).)

.~I.) P .J)l;;.:>1 ~j..:."tl).) ~ ,J.,.!, JI,.., .))'¥'..:."tl).) Ji~ ..sw...:.1 p I..J""t

WLo).) j.);5' ..s~ I) ..s)~ ~ ..1.,(4 ~ ~I.) .)1.i::J;1 Ji~ ..sw...:.1 jI..s.)I..a;

~ ..)..s>y; Lol •.)..;$ I~ <.$.. ':I4..s~ ..s~y;T)~ ~ .) ~ t1,":' ';Loj ~ I)

..s)~ ~ c....,1 ~ ~I.) .)~I (S':I ),.....9 j.r. ,i'j!.) ),.....9j.r. ~Lo)
..)y./}} WLo).) .;..::..J

J~r' w1ft-'> ')~ ~..s~ y; WLo).) tjr. .))'Y').) ..sy./~ :~,:;

..)y./'$"~)}""~ ~),J~..slA.ci4jf'r' HBV DNA;:'::J'f'r'ALT
~ .$i)}"" ).)(y,Lw:...o~f',I~~)}""<I.i)Y4..s~ (I>1!y;I..sI).)w,)~c....,If'jY

J,it9..s~ y4(cl1 <I.i ~ 4, .l.i)I.) (;':144 stage: r)..b.....,::.....s~ j,~

~ .$i)}"").) .(II1).l.iy./)} L.h.).;..::..J,~ (;Y4 ~ grade y) ~i'
(~~ stage: f) ci~ ..s~ j,~ }:i JLo'; ..s~ (I>1!y;T ..sl).) W')~
,JLo';..s~ (I>1!y;I..sI)bW')~ .(III) .l.iy./)}wLo).).;..::..J ..I.,(4 •.w4 c..:.1.)

.(I1I).l.i~WLo).)c....,I~}:i stage: 'I"

* ~ ~~ ~~ yLoJ.:t I.St~ o~~b I.SIa'Jt.:t

~ c....,1 0.);5' ~b y 0-"';" 4~ WLo).) ..sly; I) j).)";""':' w~l:i FDA
-efovir dipivoxiI) ;-I.j,9.)1 ,..:."t.)j;r.:"':1 ,Wlw,}~,WTw'}?':jI.)..;;;)i.:J:'
j (Bamclude ..s)G;t; f'li 4 entecavir) ):'.jl5:.::.i1 .(Hepsera ..s}~ f'li 4 ad
.(Tyzeka ..s)G;t; f'li 4 telbivudine) ..:."t.)j~
":""OjlA...w.)l.l.it)H).)..:."t14wLo).)0)j.)J~w.)j-!~Wj}?'..s41.;..

t~ o~w'.r."!'" jjr--' <I.i ~ W')~ ).) w,}?' oJ.rA'" .c....,1 <.$..j).)

l; <s.)t..:.::.91 dl~ It. .bL,.;J I4;,f ~ J.:S...... I'~I (.utA.. o~,,) .)I;';~ <s-,+,,;:5::. *
.::')..l.i <.S}~ It. ..s!.')::' <.S~r!> .>1 ~ ~
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. ~\.J.4.5'" ..w -. 1"1
-j.r.:'u~j-'

..s~)I,....';';;I';';~,:>'y'Li~)Is.(..s~¢"t.!)..s..l,tj¢,,~IJ.~>..slA.j)l~

)~ ci))lS<\.; j,~ 4 L..,I ,.;.;10">":" ";";lJ! r..j,.9~T ..s'J4 ..slA.jj~ 4 ~,:>j}>J jl

·~~~t)..s.r.L5' 6.:;-,:>'y'Li~}~ (I"}'~ ,. ';';Ijj) ..,...0-<>J-o..:.:..;;~

t)..s'J4JL...::>I!))~~~jJ.)Ij)~'~~j~'J~J-o~~
~ ..,...,rr'~"" r..j,.9~T jI ~r' ~~,~'J ...:.......,1 (.$!.,;I~ ..::.....,lA..o .)~I~

4.5"'r' ~?-,.; '.M-!~ ~~,~'J jI ~ r..,~1 '~":'4.5'" V"jr.., 4.5"'r'

'r..,,.9~T <\.; (.$!.,;I~ ..::.....,lA..o ~),... ,~I.Ji 0,)1.&; ..l..:S4.5"'..,...,rr' I) HBV DNA
. ..:.......,I~~,~'J jlrS ..:..w.~,,&i 'r..,~1
.)1)~;SI,.;.;}~\.5-'.'J4)~ ~ ~~,,&i 'r..,~I'.r..,,.9~T ..s,}~ <\...J

I"w 4)..s~r..,,.9~T'I.r->I ..;.;).;.; I) lA.,}~ ~I ~ ..s1.r.l"j'J .)Lo \.5-'.wl,:> ~1r..1

I"w ...:.......,1 d}' }} V" r--~ )~ LJ'j} ~ 4 .)1r.. 1)~ (Adesera ..s}:.:u
.::..WI.k.o)~ Adesera .)~",;;.-., 0">":"1"~1 Hepsera ..s').Ji.r..,,.9~i .::..WI.k.o
)~)~)~~ ~~<\.;r.u <\.; 6.:;-,:> 4.), •..:.......,1 o.l..!..i ~\j...;J~

44A><\.; ~.)I)~.)Lo)~)~;';' Adesera..l....!)4.5'"p<\.; '.r->IJL..~J,..t:>

...:.......,I};.-...,...0-<>J-o
;..:.......,Ir..j 1:"':'<\,;..,... 0-<>J-044A> .)Lo)~)~),r.i....slA.,)I~~,:.:u o~ ,j,~
.)I)~ )~ ~ )~ )4 <\...J ..s~r..; ~);; ..1..>1, . ) * I- :WT .),,)'9;.-.il
(ro}~-HBeAg.)I)~)~~)~)4<\...J..I..>I,.)*~t:;r,~-HBeAg

~ )~ )4 ~..s~r..j ~);; I"}"H lA- :(Pegasys) Wi.),)~

~1),>';';lj')I"}'~I" :~~,~'J
~1),>';';ljj)I"}'~I' :r..,,.9~T

~I),> ..s,)~ ~..s ~I)~ ..s1.Ji ~I),> .;.;Ij,) f'}'~ '/0 :r..,~1
~~,~'J <\.;1",lA..o..s ~1)~)~';';lj,)I"}'~ I ,';';Io~;s.:,,j.J"""AI.5""'r..j~

·~44.5'"
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. ..I..!..aI,>O..:lI..:l~':; •.J ..)..:l..;:..~J~..:l),...)..:l.s~.s~)..:l

~- HBeAg t." jt ~.;.,.ojoo ~~ IJt..>J')

liaJT W'},r.i, . ..:l)'1)1S <I.iW'}"o"!'/0-< I.sI)'1w'':;<.5'''')),s'J..".s,)b~ jl~yJb
.(r") . ..:l~<.5'" W'}"'''!'/ zrr )..:l (HBeAg loss) HBeAg w..l..!. ~ ~,...
t<->4 WLo)..:l <I.i f'+! ·.?~4 HBV DNA, ;;':14 ALT .s';I..:l wl).",,!,/
..:l,..l.> ~ )..:l y;, w,}~ 4 HBeAg w..l..!. ~ w'.r.-o .(n).~..:l<.5'"
~~,... ..:l;l,... zn )..:l y;, 0-<..:l,~':14 .ul......~ WLo)..:l .(yV) •..:;....,1 (I.rf)
~ ",)lc;. <I.i HBeAg w..l..!. ~~,... y;, ..:l;l,...I.IV )..:l, HBeAg w..l..!.
6.....J l:; WLo)..:l .....bl ,(rA) . ..:l"':'<.5'" (HBeAg seroconversion) HBeAb w..l..!.
.s~)..:lt,. J.i.1}1 ~,... JI...... ~ l:; , .s~;..:l1'· J.i.'}1 ~,... JI......
(f· , y~) ...:l"':'<.5'" HBeAg seroconversion
";:"~<I.iJ....9r"'" ,..:l;',...1.11' )..:lJI........s:,.. ..;:..~<I.i0-<~,~':I ....9r""'.uLA.....6
(f1) •.l.:S<.5'" !S-,;I~..:......,LA.., ~~I..:l;l,... ZF''1;..:l JI...... ~

seroconversion, lrf )~ HBeAg loss~,... fl,,.i..:lT 4 .ul........s:,.. wLo;..:l

seroconversion ~,... ,}.:. 0-<' 4 .u1......6.....J WLo)~, w'}"'"!'I1.W)~ HBeAg
4fl,,s~T <I.i ..st,;b ..:......,LA.., ~;I,... wl.r.-o ,(1"r) . ..:l"':'<.5'" wG~ 1.'fF' )~HBeAg

jl •..)',,'Ol 11 <I.iwLo)~ JI......6.....J jl ~J w'.r.-o.), ,..:;....,')~L; },.,......wLo)~JI........s:,..

wLo;~ JI...... ~)I ~ 4S ";I;~)~ .(1"1")...I...J)<.5'" lr'l <I.i WLo)..:l JI...... ~

~0~)~!S-,;I~..:......,LA..,J.i.'~~L!..l.i;l~!S-':I4HBVDNAw~
(n ,ff) . ..:;....,1

~IS ~,... )'11)'1 o..:l jl ..r.,; , ..:;....,1 0<.~,~':I jI f4.,3)4:-I fl,1S:.;:j1

W';~ lH )~ ~ fl'~' 4 .ul......~ WLo)~ ~I ...:l"':'<.5'" I"r HBV DNA
loss ~,... y;, J 4 .u1......6.....J WLo)~ .(1"t.} . ..:l"':'<.5'" HBeAg loss~,...

w';~ l'l- ;~ ~ HBV DNA peR, W')~ zrr)~ HBeAg

jIS~)""~ ~4o~;SJ ..:;..jt:!)~~~,,....)'~.;S ~I}.o~)~ .('I"r).~~.!<.5'"
)~ Lol .(fY) ..::......1 c..w...;"';';i?' 0Lo)~ Jl...,~ jl ~)"!,ts;.::.;1 4 (..S!!,)~ ..:.:......,Ui.o

jl ~ .)"!,ts;.::.;1..:;..j4)~ ~),...,.)~ •.lj~jo! f"'Ui.o ~~,,....)' 4.! ~ jl';s ~I)~

4.! ..:.:......,Ui.ozn 0Lo)~ Jl... <I.....J jI~, (fA»)"!,ts;.::.;14.! ..:.:......,Ui.o Z"l 0Lo)~ Jl...,~
~l>Jl> )~01,;~)"!,ts;.::.;ls)'4~4.!~';4.('I"~) ...::......lo..l....!,"';';i?,0 T

, S)-M> ...,..l...1 )"I )"!j ~,; .~~ ~,; 01)"!I )~ I) ,)~ ~I jl J,......." c~lA:.:......1
. ..::......lc~c~LoT J.il;s~I#, )'4)~ o~~~.u.I":'

H4~1~ 01)~)~ .~-HBeAg t'; jl.·,-'4l;A> 0Lo)~SI)"l :...,.,...,,:;

4. (~IF 1.51)"1> WT 0l,s~1 jI o~lA:.:......I.;;)'4 ALT ,;;~l; HBV DNA
)~ .(II) ~~<.5"'~'; 0Lo)~ J,I.h> 01~ 4.! (~fA 1.5 1)"1> WI 0,)~
. ..::......I~) 0Lo)~ J,I.h> 01~ 4.!)"I.,,s~T jl o~lA:.:......1'01)~)"!l...
~ oLo";"":' ,~,.:. ~ HBeAg.;S ~I~ ",""I~I ~Loj t:; ..I.t.41))"!,,s~T4 0Lo)~

S.,r.$cjl.ljI.~,)~..:.:......,Ui.o'.;"I.t~Jt...:.>1 <..5'""))"1 ~ ·(1)..l..!4 ",",,1~1#0T jI

()"!,,s~T ~Lo) ~I),> slA>,)~ 4 0Lo)~ J~)~ cLo ~ ~ HBV DNA H

.(II) ~":'<.5"'...,.,...,,:;

~ - HBeAg t,; jt ~ ~~ ~~ ~LoJ,)

0,}~I.~)"I}S 4.!r.JI)~ ~ISI)"l01<j1<.5"'I)c~~b S,)~..;....:. jl~~
Jl> ~14 '~~<.5'" ~ 0Lo).:. S~I)~ I) 01)~ Z"l·t:; f· 0Lo)~ 4.! t;.w4 WI
zr·t:;"·).:.~.;S S)~4.!..::......1~)~'0Lo)~~jl~S)~':'","~),..,

SlA>o.x..;S~~ .(fl,f')'~~<.5"'c..l.t.~0Lo)~~jl~I",I-M>t;.w4'01)~

0Lo).:. ~-M> :jI..>..:J)4-c: ~-HBeAg 01)~).:. 0,}~1 4.! f",I-M> t;.w4

f')'rs 4..r-' '0Lo)~S'))"I~}iT ~r"0~JLo; .(Jl...,.:.t:;~) ;;~)'~

-HBeAg 01)~).:. .~-HBeAg 01)~ J'>I.>)"I.;S ..::......1 ~~ 04L.:. .(fl,

0,}~1 4.! f",I-M> t;.w4 c.x..;S~~ ALT 1.5)/4 <.5"'r" ~ ~

1",1-M>~j,J')"I.,t;.w4~""#0,}~4.;Jl...~0Lo)~.(f\,f·) . ..l....!,4~
)Jb ~ "))~ jl zrr ),:; (',)1.0)':; ~ jl ...,...; JL... ,,:; ~ HBV DNA)
01.0),:; .J-J)1..5'" ~ "'-I .,:;~1..5'" 01}...,~ jl ZP ),:; HBsAg 0..1..!. ~~,...

401.0),:; "'-I ~ ";1~,:;J-" ..:.r..,:;,.t;:-,,'i, w')~ IS,)I,:;,,:; 4~;

~ 0,)rl "'-I ~~"::"""I;5'::' w~\"'!' .(fr)·..1..!.4 ~1...l.J .s..~"'-I w')~
lib ~I)F
"c.i· ....L...·1 "'~ - -l..JI:. . ......... D .......:ic.i.
)r--'y~. V U - J . - , , )L · u·1)L...." ',.11'" e.

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..s .,s;)'P")..) . ..:.........1 ~li r-,,9..)i 4 wl,.")..)"::"J,,,o J~ . ..)~ JrS wl,.,,)..)
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DNA0~r-,~T4wl,.,,)..)JL..,Ot;'fjl~..siSj'J.r.--'~0'J4e1)..)01':;1S"

~1~~,:;4~1 ...),! ~1)wl,.,,)..).bL:::>14 •...I..i)..)JI,.,,; ALT,~ HBV

jI ~ ~I)~ ~ 4 ,..);I..)..)~, w~~.:".:.1 zr· ..)'J~ )..) is)~..)~ Jlo..::.>l
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(4,1)..I.ii..oI")jA>..l..?~.jl,r-oS ~~) ,. iS~h~~)~r jl,r-oS ~~o...l..il,."

(primary non-responder) 01,.,,)..) ~ ~l;..;jL9 •.l..!>4 0..)';":' I~ ~\S

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401,.,,)'::. is'J))'I HBsAg ..s .,s;)'P" )..) . ..:.........1 ~li ..;.>...)'J~)' 4 01,.,,)..)
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(r· ) •..:.,)15"';'14..l..i":'15" ~,)..:. ..::.....,lA... )~..:. <IS I.Sj'r-oW ..J1}....-::-u..:.

~,.;) ..:.....,LG... •..:.I..:.)}.#.l.o ~,)..:. ..:.....,LG... 4 ..JIJ.o,,!:!)":' ~41) ~.~""""

..:.....,lA...o.x.:S..:.~I ..J~u~<IS ":''':'I5''J)tbII.S..:.)I~o\.; (genotypic resistance)

Lt. peR 4 (0!...:.,~'1J~ J~..:. 0\.; YMDD ..J~u~ JI;.., ..J'~ 0\.;) ~,)..:.
(virologic breakthrough)..JL..)":'15'))":' ~),J')'I.,..:."" ...:.,.:. .;.jLt._~":'I.S~,)
;:.;; ,..::......1 ..rlr..,";';" 15')":' J ~ Jl.:> )..:. )~ <IS ":''':'15'' J)li.>II.S":')~ 0\.;
15'))":' ~ ..rlt.!' ~ JJiI..l!> 0\.; ~ jlljI o..:.)I..r.,; HBV DNA 15"r'
(biochemical breakthrough) ..JL..)":'I.S'))":' ~~"""'..:."" ''':'')15''';'14 ..JL..)..:.
..JL..)..:..,:r-> )..:.i..:.~'..JL..)..:.4..J...I..1.JL..; jl.....,...;ALT <IS ":''':'I5''J)tbII.S'':')~o\.;
.~":'JI?lh~jll)breakthrough, Relapse ojl, ,..:...::......If'j'1.(r1)•..:.,jI 'lI4

DNA 15"r' ~ 0!...:.,~'1J~.,:r-> )..:. <IS I.S)~ ..:.)~)..:. JI;.., ..JI~ 0\.;

.ci) '14 HBVDNAI5"r'~ ,)":'0!.I~jl.....,...;..;.l.o,~I..:.~l; HBV

I.S)~ ~)..:. •..:.,.:.~..,..~ ~,)I..:. ..:.....,lA...,..::......1 0":';,5'..:."" I.S)~
...:.,.:. HBV DNA ":'~..J.l.oT i.ft\l;~~0!...:.,~'1..:.~tl~..::......I~
DNA 15"r' ~ •..JL..)":'I.S,))..:. ~)j1lr..,":''''' 0\.; ~ ..JI)~I)":' <IS .)l.:> )..:.
.":',)15" '14 0!. ..:.,~ 'lIJ~.,:r-> HBV
jl.....,...;, ~,.;j..::.....,lA...I~I •..l..i,.:.I5"~,)..:...::.....,lA... )~..:.<IS u;il)~)..:.
t)~~..:."" (JL.u ,..:.~ Lt.oL..~ jI.....,...;) ~~)..:. ,~jj1,)'1.,..:.",,";.l.o

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I~ ~ HBV DNA •.)t..'l,,*,,,'i t,;-!> jl ~ J,I olo ,j-!; )..'l 45 ,.Alo.::-!
HBV DNA 0lo)..'l t,;-!> jl ~ olo,j-!; 45 ;sil)lo.::-! lol ,c.......I1.A ~ ..l..:..:S
.)t..'l,,*,,,'i <\.i o~i JI...,., ..>..:..:: )..'l1.H Jl.....:.:>1 <\.i ..I..i)I..'l \.,••• copies/rol j1 ~
;,...)t.lS .)t..'l,,*,,,'i <\.i f',UL:. 01)...~ 0lo)..'l )..'l )"!,,s..'lT .(y\").";":' ..I.al,> r,UL:.
j,)'! ~¥' ,.)t..'l,,*,,,'i <\.i r,UL:. 01}.,,~)..'l ~~<\.i)"!,,s..'lT J..}"""A .(y'f).c.......1
J..}"""A 45 .)l>)..'l •..'l~\.5""o~ JI...,., ,..'l.)<>)..'l..'l;1¥, 1.\0)..'l)"!,,s..'lT <\.i..:....:.,UL:.
~¥' ~)"!,,s..'lT <\.i ..:....:.,UL:. ..'l)¥,iS..I...:»..'l" ~lS .)t..'l,,*,,,'i ')'!.,,s..'lTOt..j-oJ'>
0loj-oJ'> J..}"""A •.)t..'l,,*,,,'i <\.i ..:....:.,UL:. )~..'l Ol)lo.::-! )..'l.)tI)'!L:.; .(y() •..'l..'l}'\.5""
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jl45 ~\.5"" ..'l),>),! ;si1)L..,.,; 4 ~ 4~ <\.i ~ OI)L..,.,; ..s1\,(j)1 rlS.a oLf

t,;-!> iS l)'! is.) O~~..)..jl , ..)..j1~1..'l ~ ..s-?~)..'l ~ is)lo.::-! I~I
OI...!..,>.1 iS l)'! ~ )1 0~ lol .c.......1 ~I..)..j ..'l~, ~T iS l)'! \.S'"'"',)"!,..I...Q 0lo)..'l
~ )..'l ...)..jle";":' r,UL:. .)t..'l,,*,,,'i <\.i r'>l> Jl> )..'l •..'ly. 0";":' j.!.~ .)t..'l,,*,,,'i
m ...'l;S....A.9,:;..o I) 0lo)..'l Oly\.5"" ,c.......I#..s1.)t..'l,'*'"'i cbi\t,.....,..., ;si1)L..,.,;
HBV DNA H , is~ iS~;;T iS~ejl..)..j1 4 0 1)lo.::-! .)tl ~4 ~I .(YV ,
cbi jl ~ is~ is)lo.::-! ..'l~ jI is..'l)¥' elf I),!.) •..)..j~ )} is~ ..::..:..:;
)..'lc.......I~..>..t.(m.c.......lo..;..:. "';-;l:! .)t..'l,,*,,,'i <\.ir,UL:. Ol}....,;/)..'l.)t..'l''*''''i

<\.i ..:....:. ,UL:. 0..'l1..'l t) ~)!J-'" )..'l •j,r--'"' ~ is~ ciAt j,~ ).::::-..'l OI)L..,.,;
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"} ~ ":""'jLi.. j,)'!)1 ~";;.J.A t:; 1S-4-"J~ ~.:.,~'1.jru..:.......1 ~
.:.~ (wild type virus) .,lJlo.L!..J f"Li.. ~ ~'y:!' jl ~....,,sr'~""
0 ..1..I)':'ci4.~f"Li..IS~'Y:!'~ .0l",j.::.....:.J,f jl ~ ~1l",1.(y~)
(v.) . .:.j-!..l..lbI#,.I.;...o.:.,.....IS-4-"J~~.:.,~'1.jru ,.,lJ~($"..,..J\i.)~
01)~).:.Jio:!~l",I.(V') . ..:.......I;;...~.:.,~ '1 ~f'jLi..01)~)':'}!-l y:!,ts:.:.:.;1

JL....,.:. jI~01)~jll,\).:. x,ts:.:.:.;1 ~..::.....,Li.. j,"),!~",,'~':',~'1 ~f"Li..

.:.~,..:...Lc:.~...,...; .(r~) •.:.~($"0l",).:.JL........., jl~.:.},... jl lrl' ).:.,(1"J')0l",).:.

~l.:.o ....,tx:..il x,ts:.:.:.;1 .,).:. ,.:. ~10-::I (cross resistance) JiLQ:.:... ..::.....,Li..
·~4~ ~.:.,~ '1 ~ i"'Li.. 01)~ lSI)'!

~ ..::.....,Li.. )L::e-.:. 01)~ 0l",).:. ).:. ~l.:.o IS')':' (tenofovir) x,,g~

.~.:.,~'1 ~ f"Li.. 01)~ IS,) Yo o~f'~I..:.Wlb.o).:. •..:.......1 ~.:.,~'1

o~J).:. .:.~($" uf=I~ .(vr) . ..:.......1 o':'j-! ;;;;... ,.rt,i}!-l x,,g.:.T jI y:!,,g~

•.:.~ y:!,,g.:.T ~~G:- ~.:.,~'1 ~ f"Li.. 01)~ 0l",).:.).:. x,,g,:.:: ...s:,...:.;

...:.......10.:.p ..::....94.).:.)~ ~I ~ I) FDA <I.,t~b x,,g~ j~ ~I
HBV DNA y.;; ISlo),':' J p .~.:.,~ '1 o~.j ru 01)~).:. '"*,,,,':;
.:.}'=- .:.},... 0':''; I~ ~ real time peR if,) 4 ()4 S-.r. ol", J-!> ;A'~;;)
, .,lJ1~1.:. IS..!...,S ~ IS)~ 1.J.:41 jl ~ ";I)~).:. .(II)..:.......I (')'1 S-.r.j';,x,
0 ':;($'' •..:.......1 ~1.,lJ .:.~, ~T lSI)'! 0l",).:. t,"':' lSI)'! 1S,i 0~ts:...,lJ1
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4 ..l..t4 ";I)~ ~ . .:.,; ~ S-.r.j';,x, .:.}'=- 0.:.1.:. t) jl ...,...; I) ~.:.,~ '1
..:.......1~...l..!·(II).,lJ~IS~ HBVDNA($"r'~,ALT ISlo),.:.Jp

).:. ~I .~ ..::....94.).:. x,,g.:.T";I)~ ~ ..l..t4 IS..!...,S 1S)~..l..t..l..!.:i ..:.),...,).:.

•.,lJI~I.:. j,r--' 4. IS..!...,S 6..::t:fJ Jili j,~ ~.:.,~ '14 0l",).:. ,..l..!)':' ~ ";I)~
t,":' ;;.:.,j I)X,,g.:.T, ~W ~ S-.r.j';,x,':'}'=- 0.:.1.:. t)jl...,...; ..:.......I~
x,,g.:.T ,~.:.,~'10l",}o.Il>.jru .~.:.,~'1 ~ i"'Li.. 01)~).:. .(II) ~
,(II) ..:.......1y:!,,g.:.T 1S4-"J.jru jI~

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)I....,....; w;l~ •.::......,1 ).;.L.; )~ ,:'}A)';' JL.... ~ 4)1'.,";';'1'4 \,5:\,).;. ..::.....,lAA .;.),..
.(rr) . ..l....o)1S'" 1.",\ '4 wL..).;. JL.... ~jl....,....;, 1.1\ '4 \,5:\,).;...::.....,lAA wL..).;. JL....~

\,5:\':14 HBV DNA ~ wL..).;. JL.... ~jl....,....; <IS' ~I;L,,"=-! ~I Jl.o.;:.>l

u./lb..o j~ "-::-}'I.{n) •.::......,I~ •..l..:..:SI~ \,5:\,;'.;. ..::.....,lAA.~).;. •..l..i)';'
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Guidelines for the Management of

Chronic Hepatitis B