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Hepatitis C in Pakistan

Rashid A. Chotani
Assistant Professor & Director, The Global Infectious Disease Surveillance & Alert System The ohns !o"#ins $loomber% School of Public !ealth

A Historical Perspective
&Infectious' (iral he"atitis &Serum'
A )

)nterically transmitted

$ D

Parenterally transmitted other

The Hepatitis C Virus

S"herical, envelo"ed, sin%le+stranded R*A virus ,amily ,laviviridae !C( may "roduce - . trillion ne/ viral "articles each day R*A "olymerase lac#s "roofreadin% ca"abilities )ncodes a sin%le "oly"rotein of 01.. amino acids that is "rocessed into .1 structural and re%ulatory "roteins

The Hepatitis C Virus

A sin%le !C( floatin% amon% he"ato+ cytes

!e"atitis C is a %lobal health "roblem

Hepatitis C: Basic Facts

affectin% over .21 million "eo"le /orld/ide. There is /ide %eo%ra"hic variation in both "revalence and %enoty"e distribution of he"atitis C virus on a %lobal level. Transmitted3
$ody fluids Parenterally

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

liver disease and he"atocellular carcinoma. Des"ite a declinin% incidence of ne/ infections, the burden of disease, both in terms of mortality and in terms of cost, is e4"ected to increase over the ne4t decade.

The "revalence is increasin% /orld/ide 5!6 estimates - 711 million infected, 0.08 of the /orld9s "o"ulation Infection due to !C( accounts for :/orld/ide;3 718 of cases of acute he"atitis 218 of cases of chronic he"atitis <18 of cases of end+sta%e cirrhosis =18 of cases of he"atocellular carcinoma 018 of liver trans"lants. .21 million he"atitis C virus :!C(; carriers "resent /orld/ide 0 to < million ne/ cases "er year

Prevalence of HCV Worldwide

Features of Hepatitis C Virus Infection

Incubation "eriod Avera%e =+2 /ee#s Ran%e 7+7= /ee#s Acute illness :>aundice; ?ild :@718; Case fatality rate Ao/ Chronic infection =18+BC8 AgeChronic he"atitis related .18+218 :most as4; Cirrhosis DC8+718 ?ortality from CAD .8+C8

Chronic Hepatitis C Factors Promotin Pro ression or !everit"

Increased alcohol inta#e A%e 01+<E years at time of

Those infected at a youn%er a%e have

much better "ro%nosis

!I( co+infection 6ther
?ale %ender Chronic

!$( co+infection

!erolo ic Pattern of Acute HCV Infection with #ecover"

Sym"toms FG+ !C( R*A

anti+ !C(



*ormal 1 . 7 0 < ?onths C = . 7 0 Hears <

Time after )4"osure

!erolo ic Pattern of Acute HCV Infection with Pro ression to Chronic Infection
Sym"toms FG+ !C( R*A

anti+ !C(



*ormal 1 . 7 = . 7 0 0 < C Hears ?onths Time after )4"osure <

!ources of Infection for Persons with Hepatitis C

Se4ual .C8 In>ectin% dru% use =18

Transfusion .18 :before screenin%; 6therI C8 Jn#no/n .18

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

Source3 Centers for Disease Control and Prevention

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

GDP "er ca"ita :Intl L, 711.;3 7,.<= Aife e4"ectancy at birth ?G, :years;3 =...G=..= !ealthy life e4"ectancy at birth ?G, :years;3 C<.7GC7.0 Child mortality ?G, :"er .,111;3 .1CG..C Adult mortality ?G, :"er .,111;3 772G71. Total health e4"enditure "er ca"ita :Intl L, 711.;3 BC Total health e4"enditure as 8 of GDP :711.;3 0.E

Burden of diseases in Pakistan

!tudies in Pakistan have found HCV:

=18 amon% liver cancer "atients

:Ahmed et al., .EEC;

C.8 amon% beta thalassemia ma>or "atients :Ahmed et al., .EEC; <=8 amon% chronic liver disease "atients :?u>eeb et al., .EEB; .B8 amon% cirrhotic "atients :?u>eeb et
al., .EEB;

718 amon% commercial blood donors :?u>eeb et al., .EEB;

#isk Factors
Persons In>ectin% dru% users Reci"ients of clottin% factors made before .EB2 !emodialysis "atients Ris# of Infection !i%h !i%h Intermediate Testin% RecommendedM Hes Hes Hes Hes Hes

Reci"ients of blood andGor Intermediate solid or%ans before .EE7 Peo"le /ith undia%nosed Intermediate liver "roblems

#isk Factors
Persons Infants born to infected mothers !ealthcareG"ublic safety /or#ers Peo"le havin% se4 /ith muti"le "artners Peo"le havin% se4 /ith a steady "artner Ris# of Infection Intermediate Ao/ Ao/ Ao/ Testin% RecommendedM After .7+.B months old 6nly after #no/n e4"osure *o *o

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

Anti+!C( Prevalence
NC8 + !i%h
...+C8 + Intermediate 1.7+.8 + Ao/ 1..8 + (ery Ao/ Jn#no/n

#isk Factor:

Unsafe injections .EE03 Auby et al.

=.C8 antibodies "ositive for !C( in !afiOabad, Pa#istan Sho/s an increased "revalence in Pa#istan com"ared to /orld ,ollo/ u" case control study to identify ris# factors Positive individuals /ere B.7 times more li#ely to receive N C in>ection "er year

.EE<3 Auby et al.

#isk Factor:

Unsafe injections .EEC3 Aamir aved Phan et al.

Investi%ated relationshi" bet/een he"atitis $ and C and in>ections in "eri+ urban Parachi <<8 he"atitis C "ositive Those /ho received more in>ections /ere more li#ely to be he"atitis C infected E<8 of the needlesGsyrin%es /ere reused

#isk Factor:

CDC found that in Pa#istan, 28 of those /ith tattoos /ere "ositive for !C(

#isk Factor:
Body Piercing

In Pa#istan, 28 of those /ith body "iercin% tested "ositive for !C( :Auby et. al;

Tests for HCV: Virological markers

Detection of !C( antibodies

)nOyme immunoassays :)IA; )nOyme+lin#ed immunosorbent assays :)AISA; Detect a mi4ture of antibodies directed a%ainst various viral e"ito"es Phylo%enetic analysis can distin%uish !C( ty"es, subty"es and isolates on the basis of avera%e seQuence diver%ence rates SeQuence+based assay testin% for ty"e+s"ecific antibodies /ith a com"etitive )IA :so+called &seroty"in%';

!C( %enoty"e determination

Assessment of !C( re"lication The "resence of !C( R*A in "eri"heral blood is a reliable mar#er of active !C( re"lication !C( R*A is detectable /ithin one to t/o /ee#s after infection !C( R*A levels are stable over time in "atients /ith chronic infection :*%uyen TT, et al.; The !C( R*A level may increase sli%htly after several years of chronic infection. !C( R*A can be detected andGor Quantified in serum or "lasma by means of various cate%ories of am"lification techniQues

Tests for HCV: Virological markers

!C( S"ot Test

$ia nosis of HCV Infections

Acute he"atitis C

Should be tested for anti+!C( by means of )IA Detection of !C( R*A /ithout anti+!C( is stron%ly indicative of acute he"atitis C Acute he"atitis C is unli#ely if both mar#ers are absent. Certain in a "atient /ith chronic liver disease /hen both anti+!C( and !C( R*A are detected !i%h o"tical density ratio in )IA3 true+"ositive result, Ao/ o"tical density ratio in )IA3 no conclusion can be dra/n because anti+!C( antibody titers may fall %radually after s"ontaneous clearance of the virus

Chronic he"atitis C

$ia nosis of HCV Infections

?other+to+infant transmission Should be based on !C( R*A detection /ith a sensitive techniQue rather than on anti+!C( detection Antibodies are "assively transferred in utero and remain detectable for several months to more than a year after delivery, re%ardless of /hether viral transmission occurs Assessment of disease severity and "ro%nosis (irolo%ic tests have no "ro%nostic value

Treatment of Acute Hepatitis C

The o"timal treatment schedule remains to be established for acute he"atitis C, and no recommendations can yet be made re%ardin% the use of virolo%ic tests in the decision to treat :!oofna%le !; (irolo%ic res"onse assessed at the end of thera"y by means of a sensitive !C( R*A techniQue If !C( R*A is ne%ative, the sustained or transient nature of the res"onse is assessed 7< /ee#s later *e%ative !C( R*A detection at this second test indicates that thera"y has been successful.

Treatment of Chronic Hepatitis C

$ased on a combination of3 "e%ylated interferon :I,*; alfa, either "e%ylated I,* alfa+7a or "e%ylated I,*alfa+7b and ribavirin

%eneral Prevention !trate ies

Communication of information about !C( to health care and "ublic health "rofessionals )ducation of the "ublic and "ersons at ris# for infection Inte%ration of "revention and control activities into "ublic health "ro%rams to3

Identify, counsel, and test "ersons at ris# for !C( infection Provide referral for medical evaluation of those found to be infected Conduct outreach and community+based activities to address "ractices that "ut "eo"le at ris# for !C( infection

Surveillance to monitor acute and chronic disease trends and evaluate the effectiveness of strate%ies )"idemiolo%ic and laboratory investi%ations to better %uide "revention efforts.

Prevention !trate ies in Pakistan

?ethadone treatment "ro%rams *eedle and syrin%e e4chan%e "ro%rams Com"rehensive ris#+modifyin% educational "ro%rams )nsurin% access to sterile syrin%es throu%h "hysician "rescri"tion and "harmacy sales of syrin%es to IDJs IDJs should be educated about3

the im"ortance of hand /ashin% before and after %ivin% in>ections not usin% the othersR in>ection eQui"ment avoidin% any contact /ith blood from other "ersons

Develo"ment of reliable, re"roducible, and efficient culture systems for "ro"a%atin% !C( Role of %enetic factors in the "atho%enesis of !C( Develo"ment of less+to4ic thera"ies and molecular+based a%ents that s"ecifically inhibit viral re"lication andGor translation of viral R*A. Directed investi%ation e4aminin% the develo"ment and "ro%ression of he"atic fibrosis )stablishment of !e"atitis Clinical Research *et/or# to conduct of research related to the natural history, "revention, and treatment of he"atitis C. )4amine the "attern of !C( disease "ro%ression in "ersons infected for at least t/o decades, includin% those infected as infants and as children

Future #esearch

Future #esearch

Analysis of effectiveness of infection+control strate%ies $etter understandin% of factors that mi%ht "redict transmission Jnderstandin% side effect mana%ement and increasin% "atient adherence to thera"y. Analysis of effect of health insurance Clearly establish the role of liver bio"sy in the thera"eutic mana%ement of "atients /ith chronic he"atitis C. International standardiOation of viral R*A titers Role of fatty liver, obesity, diabetes, and he"atic iron stores in the natural history of he"atitis C and res"onses to thera"y. $etter understand !I( co+infected "atients