jurnal reading hepatitis b
TRANSCRIPT
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Jurnal Reading
“ Present and Future Therapies ofHepatitis B: From
Discovery to Cure”
Preseptor: dr Ihsanil Husna, Sp.PD
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Background
Hepatitis B virus (HBV) is a signifcant globalpathogen, inecting more than 240 millionpeople worldwide
!oreover, the actual number o persons whoare chronicall" inected is estimated to haveincreased slightl" rom 22# million to 240million during this same period
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Natural history of chronic hepatitis B
$he course o chronic HBV inection has beengrouped into our phases%
$he immune tolerant phase
$he immune active&hepatitis B e antigen(HBe'g)positive chronic hepatitis phase,
$he HBe'gnegative inactive phase
$he immune active&HBe'gnegative chronichepatitis phase
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HBV Replication
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Current therapies of hepatitis B andmechanism of action
$here are currentl" two classes o drugsapproved or the treatment o hepatitis B%nucleos(t)ide reverse transcriptase inhibitors(*+$s) and intererona (-*a)
$he frstline antiviral HBV medications includea nucleoside analogue, entecavir. a nucleotideanalogue, tenoovir. and peg"lated -*a
(/1-*a), used as monotherap"
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$he second generation *+$s such asentecavir and tenoovir can potentl" suppressthe 3*' s"nthesis step o HBV replication,the" have a little eect on the level and
activit" o ccc3*', which has a long hal lieand can persist or decades in the inectedliver despite successul antiviral treatment
ntecavir and tenoovir can decrease the levelo HBV 3*' b" 5 logs within 6 "ear otreatment and have low rates o antiviral drugresistance
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-or patients who do not have cirrhosis or donot re7uire immunosuppresive therap",proesional societ" guidelinesrecommendtreating those in the immune active phase
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Combination Studies of Current Therapies
8ombinaton o /1-* with an *+$ would bemore li9el" to result in s"nerg" because thedrugs have dierent mechanism o action, theconcept being that inhibition o viral
replication with an *+$ ma" augment theimmune eect o /1-*
/atients receiving /1-* and tenoovir had a
higher rate o HBs'g loss than those receivingeither drug along $he" represent a smallincrease (5:) in HBs'g loss over /1-*monotherap"
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HBV Entry Inhibitors
n particulr, small molecules and antibod"based treatments are 7uite eective intreating acute viral inections
!"rclude; B, c"closporin ' and othersubstrate analogues inhibit bile salt transportb" *$8/
/reliminar" results suggested that !"rclude;B is sae and well tolerated in HBs'g positivepatients with or without H3V coinection
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HBV Capsid Inhibitors
$he" unction to d"sregulate or selectivel"inhibit either pregenomic +*' encapsidationor nucleocapsid assembl" or both $he frst othese were the phen"lpropenamide
derivatives '$56 and '$6#0
$he second group is theheteroar"ldih"drop"rimidines
n vitro studies have demonstrated strongs"nerg" when these inhibitors are used incombination with currentl" approved *+$s
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HBV Nonspesific Immunomodulatory Agents
$
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Therapeutic Vaccines
nduce su=cient anti HBV immune responsesto eliminate and&or cure inected heaptoc"teswithout undue host cell damage, prevent viralspread to new heaptoc"tes and promote long
term viral control
HBs'g based Vaccine
8"toto;ic $
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Therapeutic pipeline and Conclusion
$o achieve a more sustained and eectivecontrol o HBV nection , a combination o thee;isting HBV therapies and one or more o theabove modalities, either small molecules
drugs or biologics will be necessar"
?ith growing interest in developing andeorts to develop more eectie therapies or
HBV the challenging goal o a cure ma" bewell within reach in the near uture