Jurnal Reading hepatitis B

8/20/2019 Jurnal Reading hepatitis B

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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

Jurnal Reading hepatitis B

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