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Unveiling Hepatitis C: Causes, Impact and advances in treatment

Author: Khanna, Palak; Chauhan, Rajshree; Orozalievich, Turdaliev Samatbek; Sheebamol, Gowri; Siddiqui, Jishan; Maz, Mohammad; Rehman, Md Tanvir
Publisher: Zenodo
DOI: 10.5281/zenodo.17339055
Source: https://zenodo.org/records/17339055/files/WJBPHS-2025-0040.pdf
 Co esponding au ho : Palak Khanna.
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion Liscense 4.0.
Un eiling Hepa i is C: Causes, Impac and ad ances in ea men
Palak Khanna *, Rajsh ee Chauhan, Tu dalie Sama bek O ozalie ich, Gow i Sheebamol, Jishan Siddiqui,
Mohammad Maz and Md Tan i Rehman
Depa men o public heal h, in ec ious diseases acul y, Osh s a e uni e si y, Ky gyzs an.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 294-301
Publica ion his o y: Recei ed on 30 No embe 2024; e ised on 08 Janua y 2025; accep ed on 10 Janua y 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.21.1.0040
Abs ac
Hepa i is C Vi us (HCV) in ec ion con inues o pose a majo global heal h issue, wi h a ound 58 million ch onic cases
epo ed wo ldwide and abou 1.5 million new in ec ions each yea . This i us is a p ima y con ibu o o ch onic li e
disease, ci hosis, and hepa ocellula ca cinoma (HCC), leading o app oxima ely 290,000 dea hs annually (WHO, 2022).
The in oduc ion o di ec -ac ing an i i al (DAA) he apies has ans o med HCV ea men , wi h sus ained i ologic
esponse (SVR) a es su passing 95% ac oss a ious geno ypes. Howe e , challenges emain in mee ing he Wo ld
Heal h O ganiza ion's a ge o elimina ing HCV as a public heal h h ea by 2030. Key obs acles include low diagnosis
a es, as only 21% o hose in ec ed wi h HCV a e awa e o hei condi ion, and es ic ed access o ea men , especially
in low- and middle-income coun ies (LMICs).
This a icle e iews he la es epidemiological ends ela ed o HCV, ocusing on he dispa i ies in disease bu den and
access o heal hca e. I discusses inno a i e diagnos ic me hods, such as poin -o -ca e es ing, and emphasizes he
impo ance o uni e sal sc eening p og ams in a eas wi h high p e alence. Addi ionally, we look a new he apeu ic
s a egies, including pan-geno ypic DAAs and hei e ec s on ma ginalized communi ies. Las ly, we examine public
heal h ini ia i es aimed a enhancing HCV p e en ion, such as ha m educ ion p og ams and accina ion e o s o co-
in ec ions like hepa i is B.
By in eg a ing indings om ecen s udies and epo s, his a icle highligh s he necessi y o collabo a i e global
e o s o add ess he challenges o HCV elimina ion. S a egies ha emphasize p e en ion, ea ly de ec ion, and ai
access o ea men a e c ucial o alle ia ing he HCV disease bu den and eaching elimina ion goals.
Keywo ds: hepa i is C; Vi al in ec ion; Hepa ocellula ca cinoma; Vascula diso de s; Li e biopsy
1. In oduc ion
Hepa i is C is mainly a ec ing li e and i is blood-bo ne i al in ec ion he hepa i is C i us (HCV), p ima ily ansmi ed
h ough blood- o-blood con ac . The in ec ion can be acu e o ch onic, wi h a signi ican p opo ion o indi iduals
esponsible o ch onic li e diso de s and complica ions a e ci hosis and li e cance (hepa ocellula ca cinoma).HCV
is a single-s anded RNA i us ha belongs o he Fla i i idae amily. In ec ed indi iduals may emain asymp oma ic
o yea s, wi h some p og essing o ch onic in ec ion, li e ib osis, ci hosis, o li e cance .
1.1. E iology
Main cause o HCV is injec ing o in ec ed blood, sexual in e cou se and i can be placen al ansmission du ing
childbi h. Hepa i is C i us (HCV) en e s hepa ocy es ia ecep o s such as CD81, SR-B1, and CLDN1. mos ly in ol ed
de eloping coun ies which ha e mo e middle class and lowe middle-class amilies and hose coun ies who is no able
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o a o d expensi e ea men and euse d ug injec ions equipmen . And in his coun y’s heal hca e depa men s a en’
able o p e en o p o ide igh sugges ions and p e en ion p og ams o each and e e y side and con inuously hey a e
using unsa e heal hca e ca e exposu es. And when a T a ele s isi s, hey ha e high isk o con ac and ansmission
o such diseases like HCV and blood o blood con ac disease.
1.2. T ansmission
HCV is mainly sp ead h ough con ac wi h in ec ed blood. The p ima y ansmission ou es include:
• Injec ion D ug Use: The sha ing o con amina ed needles is he mos p e alen me hod o ansmission in many
egions.
• Heal hca e-Rela ed T ansmission: Unsa e medical p ac ices, such as eusing sy inges o ailing o p ope ly
s e ilize medical equipmen , ha e his o ically played a signi ican ole in he sp ead o HCV.
• Blood T ans usions and O gan T ansplan s: P io o he in oduc ion o HCV sc eening in he 1990s, cases
ela ed o ans usions we e qui e common.
• Ma e nal-Fe al T ansmission: Ve ical ansmission om mo he o child occu s in abou 5-6% o cases, wi h
inc eased a es in mo he s who a e co-in ec ed wi h o he i uses, such as HIV.
• Sexual T ansmission: While less equen , i can happen, especially among men who ha e sex wi h men (MSM)
o indi iduals wi h o he sexually ansmi ed in ec ions.
1.3. Pa hophysiology
Hepa i is C i us (HCV) in ec ion igge s a complex in e ac ion be ween i al eplica ion and he hos 's immune
esponses, leading o li e in lamma ion and, e en ually, signi ican li e damage o e ime.
1.3.1. Vi al En y and Replica ion
HCV mainly a ge s hepa ocy es in he li e . The i us binds o speci ic ecep o s on he su ace o hos cells, such as
CD81, sca enge ecep o class B ype I (SR-BI), claudin-1, and occluding, which helps i en e he cell. Once inside, HCV
eleases i s posi i e-sense single-s anded RNA genome, which is hen ansla ed in o a polyp o ein. This polyp o ein is
clea ed by i al p o eases, including NS2-3 p o ease, in o s uc u al and non-s uc u al p o eins ha a e c ucial o i al
eplica ion. The eplica ion p ocess in ol es c ea ing a eplica ion complex associa ed wi h ea anged cy oplasmic
memb anes, pa icula ly he endoplasmic e iculum, esul ing in he p oduc ion o new i al pa icles.
1.3.2. Immune Response and Ch onic In ec ion
The immune esponse o he hos o HCV o en ails o elimina e he i us, leading o ch onic in ec ion. The i us uses
se e al s a egies o e ade he immune sys em, such as high mu a ion a es ha p oduce di e se i al quasi-species and
he p esence o hype - a iable egions in en elope glycop o eins, which make i di icul o an ibodies o neu alize
he i us e ec i ely. Fu he mo e, HCV can al e hos immune esponses, which aids in i s pe sis ence.
1.3.3. Li e In lamma ion and Fib osis
Ch onic HCV in ec ion causes ongoing li e in lamma ion, mainly due o immune-media ed p ocesses. This
in lamma o y en i onmen ac i a es hepa ic s ella e cells, esul ing in ib ogenesis and he de elopmen o li e
ib osis. O e ime, con inued ib ogenesis can lead o ci hosis, ma ked by ex ensi e sca ing o li e issue and
comp omised li e unc ion.
1.3.4. P og ession o Hepa ocellula Ca cinoma (HCC)
People wi h ci hosis caused by HCV ace a highe isk o de eloping hepa ocellula ca cinoma (HCC). While he p ecise
ways in which HCV leads o li e cance a e no comple ely clea , ac o s such as ch onic in lamma ion, con inuous li e
cell egene a ion, and he di ec impac o i al p o eins a e belie ed o con ibu e.
1.3.5. Conclusion
The pa hophysiology o HCV in ol es a complex in e play be ween he s a egies o i al eplica ion and he esponses
o he hos 's immune sys em, esul ing in ch onic li e disease, ib osis, and an inc eased isk o li e cance . Gaining
insigh in o hese mechanisms is essen ial o c ea ing e ec i e ea men s a egies and in e en ions.
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1.4. Signs and symp oms
Hepa i is C Vi us (HCV) in ec ion can show a a ie y o clinical ea u es, anging om cases ha show no symp oms o
hose wi h signi ican li e damage, such as ci hosis and hepa ocellula ca cinoma (HCC). The disease's p og ession
can be di ided in o acu e and ch onic phases, wi h symp oms a ying based on he le el o li e damage and any
ex ahepa ic mani es a ions.
Acu e HCV in ec ion occu s wi hin he i s 6 mon hs a e exposu e o he i us, bu i is equen ly unde diagnosed
because mos indi iduals do no show symp oms.
1.4.1. Symp oms in Acu e Phase
A ound 20-30% o people wi h acu e HCV in ec ion may expe ience symp oms, which can include
• Fa igue
• Fe e
• Nausea and omi ing
• Loss o appe i e
• Abdominal pain, especially in he uppe igh quad an
• Da k u ine
• Pale o clay-colo ed s ools
• Jaundice (yellowing o he skin and eyes)
• Myalgia o a h algia (muscle and join pain)
1.4.2. Clinical Cou se
App oxima ely 15-25% o acu e cases esol e on hei own wi hou de eloping in o ch onic in ec ion. Many cases go
unno iced due o mild symp oms o a comple e absence o symp oms.
Ch onic in ec ion occu s in 75-85% o cases ha do no spon aneously clea he i us. This ch onic HCV in ec ion can
las o decades and may esul in signi ican li e damage o e ime.
1.4.3. Ea ly-S age Ch onic HCV
In i s ea ly s ages, ch onic HCV o en shows no symp oms o p esen s wi h ague symp oms, such as:
• Pe sis en a igue
• Mild abdominal discom o
• Dep ession o mood dis u bances
1.4.4. Signs and Symp oms o Ad anced Li e Disease
As he in ec ion ad ances, signs o li e dys unc ion become no iceable, pa icula ly in cases o ci hosis o li e ailu e.
These signs include:
• Asci es ( luid buildup in he abdominal ca i y)
• Edema (swelling in he lowe limbs)
• Spide angiomas (spide -like blood essels on he skin)
• Jaundice
• P u i us (in ense i ching)
• Easy b uising o bleeding due o impai ed clo ing ac o p oduc ion
• Hepa ic encephalopa hy (con usion, diso ien a ion, o al e ed men al s a e due o oxin accumula ion)
1.4.5. P og ession o Hepa ocellula Ca cinoma (HCC)
Ch onic HCV is a majo cause o HCC, pa icula ly in indi iduals wi h long- e m ci hosis. Symp oms may include
unexplained weigh loss, inc easing abdominal pain, o jaundice.
1.4.6. Ex ahepa ic Mani es a ions o HCV
HCV is a sys emic disease ha can lead o complica ions ou side he li e . These ex ahepa ic mani es a ions can a ec
up o 40% o indi iduals wi h ch onic HCV and include
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1.4.7. Vascula and Immune-Media ed Diso de s
C yoglobulinemia: This condi ion can cause asculi is, esul ing in symp oms like a igue, ashes, and join pain.
• Sys emic asculi is.
• Renal Mani es a ions
• Memb anop oli e a i e glome uloneph i is, which is ma ked by p o einu ia and hema u ia.
• Endoc ine Diso de s
• Insulin esis ance and ype 2 diabe es melli us.
• De ma ological Condi ions:
• Lichen planus (cha ac e ized by an i chy ash).
• Po phy ia cu anea a da (which leads o skin sensi i i y o sunligh and blis e ing).
• Neu ological and Psychia ic Diso de s:
• Pe iphe al neu opa hy.
• Dep ession and cogni i e impai men
1.5. Diagnosis and es ing
The e a e mainly Two ypes o diagnosis es s we do: IgG assays es i is o de ec ion o HCV an ibodies, and second
we can do nucleic acid ampli ica ion o de e mine HCV RNA in blood o in ec ed pa ien s
1.5.1. Se ological es includes
• An i-HCV An ibody (An i-HCV): sc eening es in ini ial s age o de ec an ibodies agains he HCV.
• An i-HCV by ELISA
• Molecula es ;
• HCV RNA by PCR (Polyme ase Chain Reac ion)
• HCV Geno ype Tes ing
1.5.2. Li e biopsy es
T ea men and p e en ion a e necessa y o hepa i is C includes, ea men is necessa y o cu e he symp oms o
sp eading and p e en ing li e damage. medica ions, including an i i al so osbu i and dacla as i , a e gi en. In some
cases, pa ien s’ immune sys em igh s wi h he in ec ion on hei own and hey do no need ea men . P o ease
Inhibi o s (e.g., glecap e i , g azop e i ): Inhibi he NS3/4A p o ease.
1.5.3. p e en ing i al eplica ion.
NS5A Inhibi o s (e.g., ledipas i , dacla as i , elpa as i ): Inhibi he NS5A p o ein ha is esponsible o i al RNA
eplica ion and assembly.
NS5B Inhibi o s (e.g., so osbu i , dasabu i ): Inhibi he RNA polyme ase enzyme, p e en ing i al eplica ion.
T ea men o ch onic HCV wi h pegyla ed in e e on (PegIFN)-alpha and iba i in (RBV) con aining egimens is
absolu ely con aindica ed in: Uncon olled dep ession, psychosis o epilepsy; p egnancy; se e e concu en medical
diseases including e inopa hy, au oimmune hy oid diso de s; li e cell ailu e.T ea men du a ions ypically ange
om 7 o 14 weeks, depending on he indi idual’s li e heal h.
Some o he me hods o p e en hepa i is C include
• Use o heal hca e injec ions in sa e way
• disposal o needles and medical was e a e use
• sa e y o nu ses and s a who injec needle.
• dona ed blood es ing be o e aking
• T aining o heal hca e se ices
• sa e sex by using ba ie me hods.
* HCV P e en ion Guidelines and 2030 Goals;
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The 2030 goal o Hepa i is C elimina ion is ambi ious bu achie able. Wi h global sc eening e o s, uni e sal access o
DAAs, sa e y and guidance p og ams o heal hca e p o ide s who injec d ugs, and public heal h policies ha ensu e
a o dable ea men , i can play a majo ole in p ognosis;
• P e en ion h ough ha m educ ion, sa e blood p ac ices, and accina ion.
• Ea ly diagnosis and apid access o ea men .
• A o dable and scalable access o DAAs in low- and middle-income coun ies.
By 2030, he goal is o educe new HCV in ec ions, inc ease diagnosis and ea men a es, and signi ican ly educe
hepa i is- ela ed mo bidi y and mo ali y globally.
• B eas eeding is sa e in HCV posi i e mo he . Sexual ansmission is no seen in manage nous ela ion. bu in
polygamous, si ua ion, ansmission may occu .
• -The e a e 6 Geno ypes p esen in Hepa i is C i us and Geno ype 1 is mos common ype o Geno ype in USA.
• Hepa i ic c is mos common cause o ch onic hepa i is. While Hepa i is E is mos common cause o Acu e i al
hepa i is.
• In case o Hepa i is c 85% case becomes Ch onic. Ou o 85% cases, 25% leads o Ci hosis and End s age li e
disease and isk o hepa ocellula Ca cinoma inc eases.
• E en wi h no mal o modes ele a ions o Amino ans e ase in HCV inc eases isk o P og ession o Ci hosis
so An i i al he apy is necessa y he e because i ci hosis becomes decompensa ed hen mo ali y a e
inc eases.
2. Geog aphical dis ibu ion
Hepa i is C i us in ec ion occu s in all WHO egions. The highes bu den o disease is in he Eas e n Medi e anean
Region wi h 12 million people ch onically in ec ed. In he Sou h-Eas Asia Region (9 million), Eu opean Region (9
million) and he Wes e n Paci ic Region (7 million) people a e ch onically in ec ed. Eigh million people a e ch onically
in ec ed in he A ican Region and 5 million he Region o he Ame icas.
Figu e 1 This image has de ailed iew o geog aphical dis ibu ion o Hepa i is C in di e en ime pe iods

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Figu e 2 Goals o he ea men o upcoming yea s
3. Resul s and discussions
* His ological indings: In ch onic hepa i is C, in lamma ion is ypically ound in he po al a eas o he li e , which can
ex end in o he pe ipo al egions. In ec ion sp ead a e he immune esponse o he i us .in lamma ion a he
in e ace be ween he po al ac s and he su ounding li e pa enchyma.Hepa ocellula ballooning, nec osis, and
apop osis (cell dea h) may be obse ed, con ibu ing o he damage o li e issue.
*Labo a o y indings: Ele a ed ALT and AST (usually mo e han 2-3 imes he no mal ange)
AST/ALT a io is ypically <1 in ch onic Hepa i is C. Posi i e es con i ms ac i e in ec ion and helps measu e i al load.
An i-HCV An ibodies: Posi i e indica es exposu e o HCV bu no necessa ily ac i e in ec ion. Con i m wi h HCV RNA
es ing. Ele a ed bili ubin: May indica e li e dys unc ion. Low albumin: Seen in ad anced li e disease.P olonged
p o h ombin ime (PT)/INR: In ci hosis o ad anced li e disease. Low pla ele coun : Sugges i e o po al
hype ension o ad anced ci hosis. APRI (AST o pla ele a io index) and FIB-4: Non-in asi e ma ke s o assess
ib osis s age.
* Imaging indings: Ul asound: Hepa omegaly (enla ged li e ) in ea ly s ages. Ci hosis in ad anced s ages, wi h
i egula li e con ou s and sh unken li e . Splenomegaly (enla ged spleen) due o po al hype ension. Asci es ( luid
accumula ion in he abdomen) in decompensa ed ci hosis.Hepa ocellula ca cinoma (HCC) may appea as hypoechoic
masses in ci ho ic li e s.
Figu e 3 To al numbe o dea hs in wo ld acco ding o age g oup based on 2024 su ey
Elas og aphy (Fib oScan): Inc eased li e s i ness (measu ed in kPa) co ela es wi h ib osis o ci hosis.
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CT/MRI (less commonly used o diagnosis); CT/MRI may show li e a ophy, po al hype ension, splenomegaly, and
asci es in ad anced disease. HCC can be iden i ied as a mass wi h con as enhancemen .
Figu e 4 S eps o sc eening o HCV done in medical ins i u ions
4. Conclusion
Hepa i is C is a ch onic i al in ec ion. p ima ily ansmi ed h ough blood- o-blood con ac . The in ec ion o en
p og esses silen ly and can cause ch onic li e disease like ci hosis, and li e cance a e 15-20 yea s o p og ession.
wi h a signi ican p opo ion o indi iduals emaining asymp oma ic un il signi ican li e damage occu s.
Wi h he ad en o DAA he apy, Hepa i is C is now highly ea able, and cu e a es ha e d as ically imp o ed. In Ea ly-
s age diagnosis and cu e can be help ul o p e en long- e m complica ions such as ci hosis and ca cinoma. P e en ion
emains key, as he e is no accine o HCV in wo ld cu en ly. en ly wi h emphasis placed on sc eening, sa e blood
p ac ices, and needle exchange p og ams. Regula moni o ing and ollow-up ca e ensu e he bes esul s o pa ien s
li ing wi h Hepa i is C.
Re iew
This a icle co e s majo i y o he aspec s ela ed o he HCV, epidemiology and p e alence o HCV, ansmission, signs
and i s symp oms, i s diagnosis and sc eening algo i hms, p e en ion, and i s ea men . I also includes p ophylaxis
and p ognosis o i s ea men . Fo p ognosis I ha e added some da as om a ious sou ces and i is qui e help ul o
unde s anding p ognosis and ou come o he disease. Resul and discussion is e y de ailed o unde s anding he
sc eening algo i hm o disease, Mo ali y a e g aph is also use ul and he Map ha shows p e alence o he disease is a
be e way o lea n epidemiology and Geno ype ise p e alence o Hepa i is C i us. In conclusion I ha e summa ised
he whole a icle and hei de ails conclusion o all aspec s.
Compliance wi h e hical s anda ds
Acknowledgemen
We a e inc edibly g a e ul o ou uni e si y OSH STATE UNIVERSITY and all o he s who con ibu ed o his p ojec . I
would also like o hank edi o ial eam a jou nal wjbphs and all he anonymous e iewe s o hei help ul commen s
on his a icle.
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Disclosu e o con lic o in e es
The e is no con lic o in e es in any o he s a emen s p esen in he a icle.
Re e ences
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