Hepatitis C Case

8/16/2019 Hepatitis C Case

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CASECONFERENCE

Dr. Waqar Munir

Clinical Fellow Year 1

Infectious Disease


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TE CASE A !" #ears ol$ E%#&tian %entle'an (nown case of$ia)etes 'ellitus an$ *#&ertension for + #ears.

e &resente$ to t*e ,astroenterolo%# Clinic - #earsa%o w*en *e was foun$ to )e &ositie for e&atitis CAnti)o$# on routine )loo$ screenin% for )loo$$onation.

e *a$ no s#'&to's at t*at ti'e/ *e $enie$ an#

*istor# of roa$ tra0c acci$ent/ &reious *istor# of an#sur%ical &roce$ure or )loo$ transfusion.

e a$'itte$ to *ain% $ental 'ani&ulation $one #ears )efore &resentation.


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On e2a'ination/ unre'ar(a)le e2a'ination an$ nosi%ns $enotin% $eco'&ensate$ c*ronic lier $isease.

is la)orator# wor(u& s*owe$ nor'al C3C/ 4rea an$Electrol#tes 5 INR.

Mil$l# eleate$ transa'inases *oweer nor'al)iliru)in an$ al)u'in.

4ltrasoun$ lier s*owe$ fatt# lier wit*out an#

ei$ence of cirr*osis.


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e&atitis C Anti)o$#6 7ositie

e&atitis C 8uantitatie 7CR6 1+9/::: co&ies;'l

e&atitis C ,enot#&e6 <

=ier 3io&s# at t*at ti'e s*owe$ Fi)rosis %ra$e F1.


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e was starte$ on treat'ent wit* 7e%#late$ Interferonin>ections an$ ri)airin for !? wee(s.

@iral loa$ after ! wee(s $ro&&e$ to +:: co&ies;'l. oweer iral loa$ a%ain >u'&e$ to


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For &e%#late$ interferon an$ ri)airin treat'ent/res&onse rate 'ostl# $e&en$s on t*e *e&atitis C%enot#&e.

,enot#&e 1 &atients *ae aroun$ !" c*ance ofsuccess wit* &e%#late$ interferon an$ ri)airin.

,enot#&e or < &atients *ae aroun$ -" c*ance ofsuccess wit* &e%#late$ interferon an$ ri)airin.


8/42

e traelle$ to E%#&t in :1< an$ too( a full course oftreat'ent wit* Sofos)uir an$ Ri)aarin for ! wee(s.

@iral loa$ $ro&&e$ to ero at ETR fro' !":/:::co&ies;'l.

oweer at < 'ont*s followu& *e was foun$ to *ae airal loa$ of 1":/::: co&ies;'l.

No S@R ac*iee$.


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W*at is t*e &ercenta%e of S@R wit* Ri)airin 5Sofos)uir


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In t*e ran$o'ie$/ o&enla)el 3OSON trial/ inesti%ators enrolle$treat'entnaie an$ treat'ente2&erience$ &atients wit* %enot#&e or < c*ronic C@ infection/ wit* or wit*out cirr*osis/ to receie one of

t*ree treat'ent re%i'ens6 sofos)uir &lus ri)airin for 1+ wee(s/sofos)uir &lus ri)airin for ! wee(s/ an$ sofos)uir &lus ri)airin&lus &e%interferon alfaa for 1 wee(s.

A'on% t*e "9 &atients enrolle$ in t*e stu$#/ 9 *a$ %enot#&e <infection.

For t*e treat'entnaie &atients wit* %enot#&e < infection/ t*e S@R1 rates were -- wit* t*e 1+wee( sofos)uir &lus ri)airin

re%i'en/ ?? wit* ! wee(s of sofos)uir &lus ri)airin/ an$ 9"wit* 1 wee(s of sofos)uir &lus ri)airin &lus &e%interferon.

For t*e treat'entnaie &atients wit* %enot#&e < infection/ t*esu&eriorit# of t*e results wit* t*e 1wee( re%i'en of sofos)uir &lusri)airin &lus &e%interferon was 'aintaine$ in &atients wit* orwit*out cirr*osis.


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e &resente$ to ,astroenterolo%# clinic after *earin%a)out new treat'ent o&tions for C@.

Is t*ere anot*er treat'ent o&tion aaila)le for *i'


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Hepatitis

Current Recommendati


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INTROD4CTION C*ronic *e&atitis C irus C@B infection is one of t*e'ost co''on c*ronic lier $isease an$ accounts for?::: to 1


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STR4CT4RE Hepatitis C virus HCVB is a s'all ""H+" n' in sieB/enelo&e$/ &ositiesense sin%lestran$e$ RNA irus oft*e fa'il# Flaviviridae.

T*e *e&atitis C irus &article consists of a core of RNA/surroun$e$ )# an icosa*e$ral &rotectie s*ellof &rotein/ an$ furt*er encase$ in a li&i$ enelo&e ofcellular ori%in.

Structural &roteins 'a$e )# t*e *e&atitis C irusinclu$e Core &rotein/ E1 an$ E e')e$$e$ in t*e li&i$%l#co&rotein enelo&eJ nonstructural &roteinsinclu$e NS/ NS


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INTROD4CTION


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INTROD4CTION


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RE7=ICATION T*e irus re&licates 'ainl# in t*e *e&atoc#tes/ w*ere itis esti'ate$ t*at $ail# eac* infecte$ cell &ro$ucesa&&ro2i'atel# ft# irions irus &articlesB wit* acalculate$ total of one trillion irions %enerate$.

C@ *as a wi$e ariet# of %enot#&es an$ 'utatesra&i$l# $ue to a *i%* error rate on t*e &art of t*eirusK RNA$e&en$ent RNA &ol#'erase.

T*e 'utation rate &ro$uces so 'an# ariants of t*eirus it is consi$ere$ a quasis&ecies rat*er t*an aconentional irus s&ecies.


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Entr# into *ost cells occur t*rou%* co'&le2interactions )etween irions an$ cellsurface'olecules.

Once insi$e t*e *e&atoc#te/ C@ ta(es oer &ortions oft*e intracellular 'ac*iner# to re&licate.

T*e C@ %eno'e is translate$ to &ro$uce a sin%le&rotein of aroun$


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T*e NS &roteins t*en recruit t*e iral %eno'e into anRNA re&lication co'&le2/ w*ic* is associate$ wit*rearran%e$ c#to&las'ic 'e')ranes.

RNA re&lication ta(es &laces ia t*e iral RNA$e&en$ent RNA &ol#'erase NS"3/ w*ic* &ro$uces ane%atie stran$ RNA inter'e$iate.

T*e ne%atie stran$ RNA t*en seres as a te'&late for

t*e &ro$uction of new &ositie stran$ iral %eno'es.Nascent %eno'es can t*en )e translate$/ furt*erre&licate$ or &ac(a%e$ wit*in new irus &articles. Newirus &articles are t*ou%*t to )u$ into t*e secretor#&at*wa# an$ are release$ at t*e cell surface.


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INTROD4CTION


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,ENOTY7E 5

7RE@A=ENCE 3ase$ on %enetic $iLerences )etween C@ isolates/ t*e*e&atitis C irus s&ecies is classie$ intoseen %enot#&es 1H-B wit* seeral su)t#&es wit*in

eac* %enot#&e re&resente$ )# lowercase$ lettersB.

Su)t#&es are furt*er )ro(en $own into quasis&ecies)ase$ on t*eir %enetic $iersit#.

,enot#&es $iLer )#


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TRANSMISSION Most &atients infecte$ wit* C@ in t*e 4nite$ Statesan$ Euro&e acquire$ t*e $isease t*rou%* intraenous$ru% use or )loo$ transfusion/ t*e latter of w*ic* *as

)eco'e rare since routine testin% of t*e )loo$ su&&l#for C@ was )e%un in 199:.


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NAT4RA= ISTORYAcute infection

e&atitis C infection causes acute s#'&to's in 1" of

cases w*ic* are 'il$ an$ a%ue/ inclu$in% a $ecrease$a&&etite/ fati%ue/ nausea/ 'uscle or >oint &ains/ an$wei%*t loss.

Chronic infection

A)out ?: of t*ose e2&ose$ to t*e irus $eelo& a

c*ronic infection w*ic* is $ene$ as t*e &resence of$etecta)le iral re&lication for at least si2 'ont*s.


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Most &atients e2&erience 'ini'al or no s#'&to's$urin% t*e initial few $eca$es of t*e infection.

C*ronic *e&atitis C can )e associate$ wit* fati%ue an$'il$ co%nitie &ro)le's an$ later wit* si%ns an$s#'&to's of $eco'&ensate$ lier failure.

A)out 1:H


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DIA,NOSIS T*ere are a nu')er of $ia%nostic tests for *e&atitis C/inclu$in% C@ anti)o$# en#'e i''unoassa# orE=ISA/ an$ quantitatie C@ RNA &ol#'erase c*ain

reaction 7CRB.

C@ RNA can )e $etecte$ )# 7CR t#&icall# one to twowee(s after infection/ w*ile anti)o$ies can ta(esu)stantiall# lon%er to for' an$ t*us )e $etecte$.


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TREATMENT A %reater un$erstan$in% of t*e *e&atitis C irus C@B %eno'ean$ &roteins *as ena)le$ eLorts to i'&roe e0cac# an$tolera)ilit# of C@ treat'ent.

Nota)l#/ t*is *as le$ to t*e $eelo&'ent of 'ulti&le $irectactin% antiirals DAAsB/ w*ic* are 'e$ications tar%ete$ ats&ecic ste&s wit*in t*e C@ life c#cle.

DAAs are 'olecules t*at tar%et s&ecic nonstructural &roteinsof t*e irus an$ results in $isru&tion of iral re&lication an$infection.

T*ere are four classes of DAAs/ w*ic* are $ene$ )# t*eir'ec*anis' of action an$ t*era&eutic tar%et. T*e four classesare nonstructural &roteins


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NS5A inhibitors NS5Bnucleotide

polymeraseinhibitors(N!"

NS5B non#nucleoside

polymeraseinhibitors(NN!s"

NS$%&Aprotease

inhibitors

DaclatasairDC@B

El)asir E3RB

=e$i&asir =D@B

O')itasir O3@B

@el&atasir @E=B

Sofos)uirSOFB

Dasa)uir DS@B Si'e&rair SM@B

7arita&rair 7T@B

,rao&reir ,RB

3oce&reir 3OCB

Tela&reir T@RB


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INDICATIONS FOR TREATMENT OFCRONIC E7ATITIS C6 WO

SO4=D 3E TREATED AND WEN


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RegimenHCV Genotype

1a 1b 4 5 or 6

SOF + PR 12 wks 12 wks 12 wks

SMV + PR 12 wks (naive or relapse)24 wks (partial/null)

12 wks (naive or relapse)24 wks (partial/null)

Notrecommended

LDV/SOF 8-12 wks,† no RB 12 wks, no RB 12 wks, no RB

OV/P!V/R!V+ DSV

12 wks! RB

12 wks,no RB

Not recommended Notrecommended

OV/P!V/R!V Not recommended 12 wks ! RB Notrecommended

SOF + SMV 12 wks, no RB 12 wks, no RB Notrecommended

SOF + DCV 12 wks, no RB 12 wks, no RB 12 wks, no RB


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RegimenHCV Genotype

1a 1b 4 5 or 6

SOF + PR 12 wks 12 wks 12 wks

SMV + PR 12 wks (naive or relapse)24 wks (partial/null)

12 wks (naive or relapse)24 wks (partial/null)

Not recommended

LDV/SOF 12 wks ! RB or 24 wks,no RB or 24 wks ! RB

i" ne#ative predictors

12 wks ! RB or 24 wks,no RB or 24 wks ! RB i"

ne#ative predictors

12 wks ! RB or 24 wks,no RB or 24 wks ! RB i"

ne#ative predictors

OV/P!V/R!V+ DSV

24 wks! RB

12 wks! RB

Not recommended Not recommended

OV/P!V/R!V Not recommended 24 wks ! RB Not recommended

SOF + SMV 12 wks ! RB or 24 wks,no RB 12 wks ! RB or 24 wks,no RB Not recommended

SOF + DCV 12 wks ! RB or 24 wks,no RB

12 wks ! RB or 24 wks,no RB

12 wks ! RB or 24 wks,no RB


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Regimen

"o Cirr#o$i$ Compen$ate% Cirr#o$i$&C#i'%(P)g# *

G!, G!- G!, G!-

SOF + PR 12 wks 12 wks 12 wks 12 wks

SOF + RV. 12 wks 24 wks 1$-2% wks Notrecommended

SOF + DCV 12 wks,no RB

12 wks,no RB

12 wks,no RB

24 wks! RB


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3AC TO O4R

7ATIENT T*e %entle'an is a SOF )ase$ t*era non res&on$er.

Current reco''en$ation )ase$ on %enot#&e states6


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REFERENCES

4&to$ate

Me$sca&e

EAS=;AAS= %ui$elines


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TAN YO4

Hepatitis C Case

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