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Hepatitis C in PakistanHepatitis C in Pakistan

Rashid A. ChotaniRashid A. ChotaniAssistant Professor & Director,Assistant Professor & Director,

The Global Infectious Disease Surveillance & Alert SystemThe Global Infectious Disease Surveillance & Alert System

The ohns !o"#ins $loomber% School of Public !ealthThe ohns !o"#ins $loomber% School of Public !ealth

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AAInfectious'Infectious'

Serum'Serum'

(iral(iral

he"atitishe"atitis

)nterically)nterically

transmittedtransmitted

ParenterallyParenterallytransmittedtransmitted

other other

))

*A*$'*A*$'

$$ DD

CC

A Historical PerspectiveA Historical Perspective

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The Hepatitis C VirusThe Hepatitis C Virus

S"herical, envelo"ed, sin%le+stranded R*AS"herical, envelo"ed, sin%le+stranded R*Avirusvirus

amily laviviridaeamily laviviridae !C( may "roduce - trillion ne/ viral!C( may "roduce - trillion ne/ viral

"articles each day"articles each day R*A "olymerase lac#s "roofreadin%R*A "olymerase lac#s "roofreadin%

ca"abilitiesca"abilities )ncodes a sin%le "oly"rotein of 01 amino)ncodes a sin%le "oly"rotein of 01 amino

acids that is "rocessed into 1 structuralacids that is "rocessed into 1 structuraland re%ulatory "roteinsand re%ulatory "roteins

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A sin%leA sin%le!C(!C(

floatin%floatin%

amon%amon%

he"ato+he"ato+

cytescytes

The Hepatitis C VirusThe Hepatitis C Virus

http://www.hepatitis-c.de/bilder/hcva.jpg

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Hepatitis C: Basic FactsHepatitis C: Basic Facts !e"atitis C is a %lobal health "roblem!e"atitis C is a %lobal health "roblem

affectin% over 21 million "eo"le /orld/ide.affectin% over 21 million "eo"le /orld/ide. There is /ide %eo%ra"hic variation in bothThere is /ide %eo%ra"hic variation in both"revalence and %enoty"e distribution of"revalence and %enoty"e distribution ofhe"atitis C virus on a %lobal level.he"atitis C virus on a %lobal level.

Transmitted3Transmitted3$ody fluids$ody fluidsParenterallyParenterally

!e"atitis C is a leadin% cause of end+sta%e!e"atitis C is a leadin% cause of end+sta%e

liver disease and he"atocellular carcinoma.liver disease and he"atocellular carcinoma. Des"ite a declinin% incidence of ne/Des"ite a declinin% incidence of ne/

infections, the burden of disease, both ininfections, the burden of disease, both interms of mortality and in terms of cost, isterms of mortality and in terms of cost, is

e4"ected to increase over the ne4t decade.e4"ected to increase over the ne4t decade.

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The "revalence is increasin% /orld/ideThe "revalence is increasin% /orld/ide

5!6 estimates - 711 million infected, 0.08 of the5!6 estimates - 711 million infected, 0.08 of the/orld9s "o"ulation/orld9s "o"ulation

Infection due to !C( accounts for :/orld/ide;3Infection due to !C( accounts for :/orld/ide;3

718 of cases of acute he"atitis718 of cases of acute he"atitis

218 of cases of chronic he"atitis218 of cases of chronic he"atitis

<18 of cases of end+sta%e cirrhosis<18 of cases of end+sta%e cirrhosis

=18 of cases of he"atocellular carcinoma=18 of cases of he"atocellular carcinoma

018 of liver trans"lants.018 of liver trans"lants.

21 million he"atitis C virus :!C(; carriers21 million he"atitis C virus :!C(; carriers

"resent /orld/ide"resent /orld/ide

0 to < million ne/ cases "er year 0 to < million ne/ cases "er year

Prevalence of HCV WorldwidePrevalence of HCV Worldwide

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Features of Hepatitis CFeatures of Hepatitis C

Virus InfectionVirus InfectionIncubation "eriodIncubation "eriod Avera%e =+2 /ee#sAvera%e =+2 /ee#s

Ran%e 7+7= /ee#sRan%e 7+7= /ee#s

Acute illness :>aundice;Acute illness :>aundice; ?ild :@718;?ild :@718;Case fatality rateCase fatality rate o/o/

Chronic infectionChronic infection =18+B8=18+B8

Chronic he"atitisChronic he"atitis 18+21818+218 :most as4;:most as4;CirrhosisCirrhosis 8+7188+718

?ortality from CD?ortality from CD 8+88+8

Age-

related

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Chronic Hepatitis C FactorsChronic Hepatitis C Factors

Promotin Proression or !everit"Promotin Proression or !everit" Increased alcohol inta#eIncreased alcohol inta#e

A%e 01+<E years at time ofA%e 01+<E years at time ofinfectioninfectionThose infected at a youn%er a%e haveThose infected at a youn%er a%e have

much better "ro%nosismuch better "ro%nosis

!I( co+infection!I( co+infection

6ther 6ther ?ale %ender ?ale %ender

Chronic !$( co+infectionChronic !$( co+infection

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!eroloic Pattern of Acute HCV!eroloic Pattern of Acute HCVInfection with #ecover"Infection with #ecover"

Sym"tomsF+

Time after )4"osure

T i t e r

anti+!C(

AT

*ormal

1 7 0 < = 7 0 < Hears?onths

!C( R*A

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!eroloic Pattern of Acute HCV!eroloic Pattern of Acute HCVInfection with Proression toInfection with Proression to

Chronic InfectionChronic InfectionSym"tomsSym"tomsF+F+

Time after )4"osureTime after )4"osure

T i t e r

T i t e r

anti+anti+!C(!C(

ATAT

*ormal*ormal

11 77 00 << == 77 00 <<

Hears Hears?onths?onths

!C( R*A!C( R*A

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!ources of Infection for!ources of Infection forPersons with Hepatitis CPersons with Hepatitis C

Se4ual 8Se4ual 8

6ther 86ther 8

Jn#no/n 18Jn#no/n 18

In>ectin%In>ectin%

dru% usedru% use=18=18 Transfusion 18Transfusion 18

:before screenin%;:before screenin%;

!emodialysisK health+care /or#K "erinatal !emodialysisK health+care /or#K "erinatal

Source3 Centers for Disease Control and PreventionSource3 Centers for Disease Control and Prevention

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PakistanPakistan Total "o"ulation3 <E,E,111Total "o"ulation3 <E,E,111

GDP "er ca"ita :Intl L, 711;3 7,<=GDP "er ca"ita :Intl L, 711;3 7,<= ife e4"ectancy at birth ? :years;3ife e4"ectancy at birth ? :years;3

=.=.==.=.=

!ealthy life e4"ectancy at birth ?!ealthy life e4"ectancy at birth ?:years;3 <.77.0:years;3 <.77.0 Child mortality ? :"er ,111;3 1Child mortality ? :"er ,111;3 1 Adult mortality ? :"er ,111;3 77271Adult mortality ? :"er ,111;3 77271

Total health e4"enditure "er ca"ita :Intl L,Total health e4"enditure "er ca"ita :Intl L,711;3 B711;3 B Total health e4"enditure as 8 of GDPTotal health e4"enditure as 8 of GDP

:711;3 0.E:711;3 0.E

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Burden of diseases in PakistanBurden of diseases in Pakistan

!tudies in Pakistan have found HCV:!tudies in Pakistan have found HCV: =18 amon% liver cancer "atients=18 amon% liver cancer "atients

:Ahmed et al., EE;:Ahmed et al., EE;

8 amon% beta thalassemia ma>or8 amon% beta thalassemia ma>or"atients"atients :Ahmed et al., EE;:Ahmed et al., EE;

<=8 amon% chronic liver disease<=8 amon% chronic liver disease

"atients"atients :?u>eeb et al., EEB;:?u>eeb et al., EEB; B8 amon% cirrhotic "atientsB8 amon% cirrhotic "atients :?u>eeb et:?u>eeb et

al., EEB;al., EEB;

718 amon% commercial blood718 amon% commercial blood

donorsdonors :?u>eeb et al., EEB;:?u>eeb et al., EEB;

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#isk Factors#isk Factors

Hes HesIntermediateIntermediatePeo"le /ith undia%nosedPeo"le /ith undia%nosed

liver "roblemsliver "roblems

Hes HesIntermediateIntermediateReci"ients of blood andorReci"ients of blood andor

solid or%ans before EE7solid or%ans before EE7

Hes HesIntermediateIntermediate

!emodialysis "atients!emodialysis "atients

Hes Hes!i%h!i%hReci"ients of clottin%Reci"ients of clottin%

factors made before EB2factors made before EB2

Hes Hes!i%h!i%hIn>ectin% dru% usersIn>ectin% dru% users

Testin%Testin%

RecommendedMRecommendedMRis# ofRis# of

InfectionInfectionPersonsPersons

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#isk Factors#isk Factors

*o*oo/o/Peo"le havin% se4 /ith aPeo"le havin% se4 /ith a

steady "artner steady "artner

*o*oo/o/Peo"le havin% se4 /ithPeo"le havin% se4 /ith

muti"le "artnersmuti"le "artners

6nly after6nly after

#no/n e4"osure#no/n e4"osure

o/o/!ealthcare"ublic safety!ealthcare"ublic safety

/or#ers/or#ers

After 7+BAfter 7+B

months oldmonths oldIntermediateIntermediateInfants born to infectedInfants born to infected

mothersmothers

Testin%Testin%

RecommendedMRecommendedMRis# ofRis# of

InfectionInfectionPersonsPersons

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.+8 + Intermediate

Anti+!C(Prevalence

N8 + !i%h

1.7+8 + o/

1.8 + (ery o/

Jn#no/n

Prevalence of anti+!C(amon%st blood donors

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#isk Factor:#isk Factor:Unsafe injectionsUnsafe injections

EE03 uby et al.EE03 uby et al. =.8 antibodies "ositive for !C( in=.8 antibodies "ositive for !C( in

!afiOabad, Pa#istan!afiOabad, Pa#istan Sho/s an increased "revalence inSho/s an increased "revalence in

Pa#istan com"ared to /orldPa#istan com"ared to /orld

EE<3 uby et al.EE<3 uby et al. ollo/ u" case control study to identifyollo/ u" case control study to identify

ris# factorsris# factors Positive individuals /ere B.7 times morePositive individuals /ere B.7 times more

li#ely to receive N in>ection "er year li#ely to receive N in>ection "er year

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#isk Factor:#isk Factor:Unsafe injectionsUnsafe injections

EE3 Aamir aved han et al.EE3 Aamir aved han et al. Investi%ated relationshi" bet/eenInvesti%ated relationshi" bet/een

he"atitis $ and C and in>ections in "eri+he"atitis $ and C and in>ections in "eri+

urban arachiurban arachi <<8 he"atitis C "ositive<<8 he"atitis C "ositive

Those /ho received more in>ections /ereThose /ho received more in>ections /eremore li#ely to be he"atitis C infectedmore li#ely to be he"atitis C infected

E<8 of the needlessyrin%es /ere reusedE<8 of the needlessyrin%es /ere reused

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#isk Factor:#isk Factor:TattooingTattooing

CDC found that in Pa#istan, 28 ofCDC found that in Pa#istan, 28 of

those /ith tattoos /ere "ositivethose /ith tattoos /ere "ositivefor !C(for !C(

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#isk Factor:#isk Factor:

Body PiercingBody Piercing

In Pa#istan, 28 of those /ith bodyIn Pa#istan, 28 of those /ith body

"iercin% tested "ositive for !C("iercin% tested "ositive for !C(:uby et. al;:uby et. al;

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Tests for HCV:Tests for HCV: VVirological markersirological markers

Detection of !C( antibodiesDetection of !C( antibodies

)nOyme immunoassays :)IA;)nOyme immunoassays :)IA; )nOyme+lin#ed immunosorbent assays :)ISA;)nOyme+lin#ed immunosorbent assays :)ISA; Detect a mi4ture of antibodies directed a%ainstDetect a mi4ture of antibodies directed a%ainst

various viral e"ito"esvarious viral e"ito"es !C( %enoty"e determination!C( %enoty"e determination

Phylo%enetic analysis can distin%uish !C(Phylo%enetic analysis can distin%uish !C(

ty"es, subty"es and isolates on the basis ofty"es, subty"es and isolates on the basis of

avera%e seQuence diver%ence ratesavera%e seQuence diver%ence rates SeQuence+based assaySeQuence+based assay testin% for ty"e+s"ecific antibodies /ith atestin% for ty"e+s"ecific antibodies /ith a

com"etitive )IA :so+called seroty"in%';com"etitive )IA :so+called seroty"in%';

T f HCVT t f HCV

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Tests for HCV:Tests for HCV: Virological markersVirological markers Assessment of !C( re"licationAssessment of !C( re"lication

The "resence of !C( R*A inThe "resence of !C( R*A in

"eri"heral blood is a reliable"eri"heral blood is a reliablemar#er of active !C( re"licationmar#er of active !C( re"lication

!C( R*A is detectable /ithin one!C( R*A is detectable /ithin one

to t/o /ee#s after infection to t/o /ee#s after infection

!C( R*A levels are stable over!C( R*A levels are stable overtime in "atients /ith chronictime in "atients /ith chronic

infectioninfection :*%uyen TT, et al.;:*%uyen TT, et al.;

The !C( R*A level may increaseThe !C( R*A level may increase

sli%htly after several years ofsli%htly after several years ofchronic infection.chronic infection. !C( R*A can be detected andor!C( R*A can be detected andor

Quantified in serum or "lasma byQuantified in serum or "lasma by

means of various cate%ories ofmeans of various cate%ories of

am"lification techniQuesam"lification techniQues !C( S"ot Test!C( S"ot Test

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$ianosis of HCV Infections$ianosis of HCV Infections Acute he"atitis CAcute he"atitis C

Should be tested for anti+!C( by means of )IAShould be tested for anti+!C( by means of )IA Detection of !C( R*A /ithout anti+!C( isDetection of !C( R*A /ithout anti+!C( is

stron%ly indicative of acute he"atitis Cstron%ly indicative of acute he"atitis C Acute he"atitis C is unli#ely if both mar#ersAcute he"atitis C is unli#ely if both mar#ers

are absent.are absent. Chronic he"atitis CChronic he"atitis C

Certain in a "atient /ith chronic liver diseaseCertain in a "atient /ith chronic liver disease/hen both anti+!C( and !C( R*A are/hen both anti+!C( and !C( R*A are

detecteddetected !i%h o"tical density ratio in )IA3 true+"ositive!i%h o"tical density ratio in )IA3 true+"ositiveresult,result,

o/ o"tical density ratio in )IA3 no conclusiono/ o"tical density ratio in )IA3 no conclusioncan be dra/n because anti+!C( antibody titerscan be dra/n because anti+!C( antibody titers

may fall %radually after s"ontaneous clearancemay fall %radually after s"ontaneous clearanceof the virusof the virus

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$ianosis of HCV Infections$ianosis of HCV Infections

?other+to+infant transmission?other+to+infant transmission Should be based on !C( R*A detectionShould be based on !C( R*A detection

/ith a sensitive techniQue rather than on/ith a sensitive techniQue rather than onanti+!C( detectionanti+!C( detection

Antibodies are "assively transferredAntibodies are "assively transferred ininuteroutero and remain detectable for severaland remain detectable for severalmonths to more than a year after delivery,months to more than a year after delivery,

re%ardless of /hether viral transmissionre%ardless of /hether viral transmissionoccursoccurs

Assessment of disease severity andAssessment of disease severity and"ro%nosis"ro%nosis

(irolo%ic tests have no "ro%nostic value(irolo%ic tests have no "ro%nostic value

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Treatment ofTreatment of

Acute Hepatitis CAcute Hepatitis C

The o"timal treatment schedule remains to beThe o"timal treatment schedule remains to be

established for acute he"atitis C, and noestablished for acute he"atitis C, and no

recommendations can yet be made re%ardin% therecommendations can yet be made re%ardin% the

use of virolo%ic tests in the decision to treatuse of virolo%ic tests in the decision to treat

:!oofna%le !;:!oofna%le !; (irolo%ic res"onse assessed at the end of thera"y(irolo%ic res"onse assessed at the end of thera"y

by means of a sensitive !C( R*A techniQueby means of a sensitive !C( R*A techniQue If !C( R*A is ne%ative, the sustained or transientIf !C( R*A is ne%ative, the sustained or transient

nature of the res"onse is assessed 7< /ee#s later nature of the res"onse is assessed 7< /ee#s later *e%ative !C( R*A detection at this second test*e%ative !C( R*A detection at this second test

indicates that thera"y has been successful.indicates that thera"y has been successful.

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Treatment ofTreatment of

Chronic Hepatitis CChronic Hepatitis C $ased on a combination of3$ased on a combination of3

"e%ylated interferon :I*; alfa,"e%ylated interferon :I*; alfa, either "e%ylated I* alfa+7aeither "e%ylated I* alfa+7a

or "e%ylated I*alfa+7bor "e%ylated I*alfa+7b and ribavirinand ribavirin

% l P ti !t t i% l P ti !t t i

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%eneral Prevention !trateies%eneral Prevention !trateies Communication of information about !C( toCommunication of information about !C( to

health care and "ublic health "rofessionalshealth care and "ublic health "rofessionals

)ducation of the "ublic and "ersons at ris# for)ducation of the "ublic and "ersons at ris# forinfectioninfection

Inte%ration of "revention and control activities intoInte%ration of "revention and control activities into"ublic health "ro%rams to3"ublic health "ro%rams to3

Identify, counsel, and test "ersons at ris# for !C(Identify, counsel, and test "ersons at ris# for !C(infectioninfection Provide referral for medical evaluation of those found toProvide referral for medical evaluation of those found to

be infectedbe infected Conduct outreach and community+based activities toConduct outreach and community+based activities to

address "ractices that "ut "eo"le at ris# for !C(address "ractices that "ut "eo"le at ris# for !C(infectioninfection Surveillance to monitor acute and chronic diseaseSurveillance to monitor acute and chronic disease

trends and evaluate the effectiveness of strate%iestrends and evaluate the effectiveness of strate%ies )"idemiolo%ic and laboratory investi%ations to)"idemiolo%ic and laboratory investi%ations to

better %uide "revention efforts.better %uide "revention efforts.

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Prevention !trateiesPrevention !trateies

in Pakistanin Pakistan

?ethadone treatment "ro%rams?ethadone treatment "ro%rams *eedle and syrin%e e4chan%e "ro%rams*eedle and syrin%e e4chan%e "ro%rams Com"rehensive ris#+modifyin% educationalCom"rehensive ris#+modifyin% educational

"ro%rams"ro%rams )nsurin% access to sterile syrin%es throu%h)nsurin% access to sterile syrin%es throu%h

"hysician "rescri"tion and "harmacy sales of"hysician "rescri"tion and "harmacy sales ofsyrin%es to IDJssyrin%es to IDJs

IDJs should be educated about3IDJs should be educated about3 the im"ortance of hand /ashin% before and afterthe im"ortance of hand /ashin% before and after

%ivin% in>ections%ivin% in>ections not usin% the others in>ection eQui"mentnot usin% the others in>ection eQui"ment

avoidin% any contact /ith blood from other "ersonsavoidin% any contact /ith blood from other "ersons

Future #esearchFuture #esearch

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Future #esearchFuture #esearch Develo"ment of reliable, re"roducible, andDevelo"ment of reliable, re"roducible, and

efficient culture systems for "ro"a%atin% !C(efficient culture systems for "ro"a%atin% !C(

Role of %enetic factors in the "atho%enesis ofRole of %enetic factors in the "atho%enesis of!C(!C( Develo"ment of less+to4ic thera"ies andDevelo"ment of less+to4ic thera"ies and

molecular+based a%ents that s"ecifically inhibitmolecular+based a%ents that s"ecifically inhibitviral re"lication andor translation of viral R*A.viral re"lication andor translation of viral R*A.

Directed investi%ation e4aminin% theDirected investi%ation e4aminin% thedevelo"ment and "ro%ression of he"atic fibrosisdevelo"ment and "ro%ression of he"atic fibrosis

)stablishment of !e"atitis Clinical Research)stablishment of !e"atitis Clinical Research*et/or# to conduct of research related to the*et/or# to conduct of research related to the

natural history, "revention, and treatment ofnatural history, "revention, and treatment ofhe"atitis C.he"atitis C. )4amine the "attern of !C( disease "ro%ression)4amine the "attern of !C( disease "ro%ression

in "ersons infected for at least t/o decades,in "ersons infected for at least t/o decades,

includin% those infected as infants and asincludin% those infected as infants and aschildrenchildren

F # hF t # h

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Future #esearchFuture #esearch Analysis of effectiveness of infection+controlAnalysis of effectiveness of infection+control

strate%iesstrate%ies $etter understandin% of factors that mi%ht$etter understandin% of factors that mi%ht

"redict transmission"redict transmission Jnderstandin% side effect mana%ement andJnderstandin% side effect mana%ement and

increasin% "atient adherence to thera"y.increasin% "atient adherence to thera"y. Analysis of effect of health insuranceAnalysis of effect of health insurance Clearly establish the role of liver bio"sy in theClearly establish the role of liver bio"sy in the

thera"eutic mana%ement of "atients /iththera"eutic mana%ement of "atients /ithchronic he"atitis C.chronic he"atitis C.

International standardiOation of viral R*A titersInternational standardiOation of viral R*A titers Role of fatty liver, obesity, diabetes, andRole of fatty liver, obesity, diabetes, and

he"atic iron stores in the natural history ofhe"atic iron stores in the natural history ofhe"atitis C and res"onses to thera"y.he"atitis C and res"onses to thera"y.

$etter understand !I( co infected "atients$etter understand !I( co infected "atients

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