HCV epidemiology WEI 20190526...

WEILai,MD.

Hepatopancreabiliary CenterBeijingTsinghuaChanggung Hospital

TsinghuaUniversity

HCVEpidemiology-Onthewayelimination

BackgroundGlobally,anestimated71millionpeoplehavechronichepatitisCinfection.Approximately399000peopledieeachyearfromhepatitisC,mostlyfromcirrhosisandhepatocellularcarcinoma.

WHOadoptedthestrategywitheliminatingviralhepatitisasapublichealthproblemby2030,globaltargetsincludereducingnewviralhepatitisinfectionsby90%andreducingdeathsduetoviralhepatitisby65%.

CurrentlynovaccineforhepatitisC.

Antiviralmedicinescancuremorethan95%ofpersonswithhepatitisCinfection,therebyreducingtheriskofdeathfromlivercancerandcirrhosis.

TargetsandwaytoeliminateTargetsforreducingnewcasesofanddeathsfromchronicviralhepatitisCinfection,2020and2030

https://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf?sequence=1, as for May 23th, 2019


Servicecoveragetargets 2020 2030

reducingnewcases

Safeinjections 50% 90%

Harmreduction:numberofsterileneedlesandsyringesprovidedperpersonwhoinjectsdrugsperyear

200 300

reducingdeaths

ViralhepatitisCdiagnosis 30% 90%

ViralhepatitisC treatment 3millionpeoplehavereceivedhepatitisCvirustreatment

80%ofeligiblepersonswithchronichepatitisCvirusinfectiontreated


HCVepidemiologyrelatedwithelimination


reducingnewcases

Safeinjections Status:Where,Who, HowmanyHarmreduction:numberof

sterileneedlesandsyringesprovidedperpersonwhoinjectsdrugsperyear

reducingdeaths

ViralhepatitisBandCdiagnosis Status:Where,Who, HowmanyViralhepatitisBandC treatment




reducingnewcases

Safeinjections 3.9%reuseofinjectionequipmentin2017

Harmreduction:numberofsterileneedlesandsyringesprovidedperpersonwhoinjectsdrugsperyear

33syringesorneedlesetsperpersonwhoinjectsdrugsperyear in2017

reducingdeaths

ViralhepatitisCdiagnosis 13.1million(19%)ofpeoplelivingwithhepatitisCknewtheirhepatitisCstatusin2017

ViralhepatitisC treatment 5millionpeoplediagnosedwithhepatitisCinfectionhadbeentreatedusingDAAsbytheendof2017


HCVnewinfection

https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-c as for May 23th, 2019

Estimatesobtainedfrommodellingsuggestthatworldwide,in2015,therewere1.75millionnewHCVinfections(globally,23.7newHCVinfectionsper100000people).

PopulationsatincreasedriskofHCVinfection

People who inject drugs;People who use intranasal drugs;Recipients of infected blood products or invasive procedures in Health-care facilities with inadequate infection control practices ;Children born to mothers infected with HCV ;People with sexual partners who are HCV-infected;People with HIV infection;Prisoners or previously incarcerated persons; andPeople who have had tattoos or piercings.


PeoplewithHigh-riskofHCVinfectionshouldbescreened

Wei L,etal.NationalScreeningandManagementofHepatitisC2014,MinistryofHealth

People with injection history of intravenous drug addictionSpecial invasive operationPatients with consistent HemodialysisChildren born by mother infected with HCVExposed to HCV patients , having hospital transmission riskPrior to emergency invasive examination

InAugust2014,theNationalHealthandFamilyPlanningCommissionapprovedaNationalScreeningandManagementStandardforHCVinfection

ThehepatitisCvirusmostcommonlytransmittedthrough:

Injecting drug use through the sharing of injection equipment;

The reuse or inadequate sterilization of medical equipment, especially syringes and needles in healthcare settings; and

The transfusion of unscreened blood and blood products.


HCVinfectionamongHIVinfection


About 2.3 million people of the estimated 36.7 million living with HIV globally have serological evidence of past or present HCV infection.

Conversely, among all HIV-infected persons, the prevalence of anti-HCV was 6.2%.

Liver diseases represent a major cause of morbidity and mortality among persons living with HIV.

HCVinfectionsexuallyandMTCT

HCVcanbetransmittedsexuallyHCVcanbepassedfromaninfectedmothertoherbaby;

howeverthesemodesoftransmissionaremuchlesscommon.


PrevalenceofHIVinfection,syphilisandHCVindrugusersinWuhan,2009–2016

HIV syphilis HCV Antibody (%

)

Xu J, et al. Disease Survellance, 2019,34:254-259

Anti-HCV sero-epidemiological study by using the remaining blood samples and data of the nationwide survey of hepatitis B in Chinese residents carried out in 2006.

Anti-HCVinChildren,China

Age Urbanarea RuralArea Total

Ntested PositiveRate(%)



1-4.9 7,232 0.11 7,505 0.07 14,737 0.09

5-9.9 5,755 0.17 5,690 0.16 11,445 0.17

10-14.9 5,656 0.39 5,900 0.14 11,556 0.26

15-19.9 1,339 0.37 1,536 0.45 2,895 0.41

1-59, Total 39,143 0.42 39,603 0.35 78,746 0.40

Chen YS, et al. Chin J Epidemiol (in Chinese), 2011,32(9):888-891.

FactorsRelatedtoHCVInfectioninadolescentsandchildren(N(%))

Factors Beijing2013-20151.3-6.1yrs.

Beijing2011-20121-17yrs.

Historyofbloodtransfusion/administrationof bloodproduct

3(10) 42 (15)

HCV/HIVinfectedmother 4(13.3)Unsafetyinjectionhistory 277 (77)Unknown 23(76.7) 31 (11)Total 30(100) 277(100)

Sun YY, et al. Basic & Clinical Medicine (in Chinese), 2018,38(8):1111-1114.Wu RR, et al. Pak J Med Sci, 2014,30(3):519-524.

HCVinfectionresultedinatleast29000HCV-infectedwomengivingbirtheachyear

StudyPopulation Timing HCVinfectionPregnancy

Children

NationalNotifiableDiseasesSurveillanceSystem,CA(1)

2006- 2014 15550- 31039 3.2-foldhigherinpercentageamongchildrenaged2to3years

Birthcertificatedata(2) 2011- 2014 proportionofinfantsborntoHCV-infectedmothersincreased68%,from0.19%to0.32%

MedicaidRecipients(3) 2011- 2015 HCVinfectionduringpregnancyincreased93%

1. Lv KN, et al. Ann Intern Med. 2017;166(11):775-782.2. Koneru A, et al. MMWR Morb Mortal Wkly Rep. 2016;65(28):705-10.3. Watts T, et al. MMWR Morb Mortal Wkly Rep. 2017;66(42):1136-1139.

HCVcascadeofcareestimatesbyWHOregion,2015

https://apps.who.int/iris/bitstream/handle/10665/277006/WHO-CDS-HIV-18.47-eng.pdf?ua=1

HCVcascadeofcareestimatesbyWHOregioncategories,2015

WesternPacific Global

Diagnosed

Totalnumber(Bestestimate,range) 2,985,000(2,815,000–2,998,000) 14,255,000 (13,166,000–14,638,000)

Proportion(%)(Bestestimate,range) 21.5(20.3– 20.6) 20.0(18.5– 20.6)

Treatmentinitiation(annual)

Number(Bestestimate,range) 144,000(141,000– 145,000) 1,503,000(987,000– 1,116,000)

Rate(Bestestimate,range) 4.8(4.7– 5.0) 7.4(7.0–8.1)

Cumulativenumberofpersonsstartedontreatment

1,169,000(1,166,000– 1,171,000) 5,495,000 (5,429,000– 5,558,000)

Sustainedvirological response(annual)

Number(Bestestimate,range) 91,000(88,000– 92,000) 843,000(795,000– 886,000)

SVR(%) 61.3(62.6–63.4) 80(75.6- 81.6)

https://apps.who.int/iris/bitstream/handle/10665/277006/WHO-CDS-HIV-18.47-eng.pdf?ua=1

FactorsimpactingSVR

Host VirusPegIFNalpha+RBV(beforeDAAera)

DAAs

Cirrhosis Viral load Genotype?Alcoholism Genotype ResistanceAssociated

SubstitutionRAS(s)

OldOther Others

A30K+L31MRASsresistanttoNS5Ainhibitors

A30K + L31M and A30K + L31M + Y93H had 3-fold higher replication capacity than WT A30K + Y93H had 1-fold lower replication capacity than WT.

Hepatology. 2018 Feb 9. doi: 10.1002/hep.29837. [Epub ahead of print]

A30K+L31MRASsinGenotype3

Sub-genotype

NS5A RASsA30K A30R L31M A30K+L31M

3a(n=31) 1(3.23%) 0(0) 0(0) 0(0)

3b(n=53) 51(96.22%) 1(1.89%) 50(94.34%) 49(92.45%)

合计(n=84) 52(61.90%) 1(1.19%) 50(59.52%) 49(58.33%)

Wei L, data on file

ComplexGenotypedistributioninChina

24Multiple genotypes

1b2b

6c

HCV Genotype1a

3b 3a2a or 2c

6a or 6b

Unidentifiable

Overall

Rao H, et al. J Gastroenterol Hepatol. 2014;29(3):545-53.

CompositionofHCVgenotypes1,2,3,6inMainlandChina

Chen Y, et al. Emerging Microbes& Infections, 6:1, 1-7, DOI: 10.1038/emi.2017.77

EfficacyofSofosbuvir/Velpatasvir inGenotype1‒6HCV-InfectedPatientsinChina:ResultsFromaPhase3ClinicalTrial

SVR

12, %

254264

Overall

8282

6262

4959

6161

GT 1 GT 2 GT 3 GT 6¨ PatientswithoutSVR12:9relapsesand1losttofollow-up(LTFU)

Wei L, et al. Lancet Gastroenterol Hepatol. 2019 Feb;4(2):127-134.

SVR:CirrhosisStatusandHCVSubtype

Wei L, et al. Lancet Gastroenterol Hepatol. 2019 Feb;4(2):127-134.

GT 3b

714

SVR

12, %

GT 3a

1719

2223

33

*1noncirrhoticpatientwithGT3awasLTFU.CirrhosisNo Cirrhosis No CirrhosisCirrhosis

Summary:eliminationrelatedepidemiology

Unsafety injection, reuse or inadequate sterilization of medical equipment, MTCT are major risk factors for new infection.

Prevention should be focused on safety injection, harm reduction to achieve elimination.

More patients need treatment

Cirrhotic patients with genotype 3b emerges as so-called “difficult-to-treat” and need new strategy.

HCV epidemiology WEI 20190526...

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