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De la eradicarea (individuala) la eliminarea (globala) VHC:
Modelare pentru un Plan National de Eliminare in Romania
pana in 2030
Liana Gheorghe
Profesor de Gastroenterologie siHepatologie
Universitatea de Medicina si Farmacie Carol Davila
Centrul de Gastroenterologie si hepatologie
Institutul Clinic Fundeni Bucuresti
De ce avem nevoie de o strategie globala pentru eliminarea
hepatitelor virale ? –Contextul Global
WHO 2016-2021 draft Global Health Sector Strategy on Viral Hepatitis, Gottfried Hirnschall, Director of the WHO Department of HIV and Global Hepatitis Program
• Major global public health threat
• Progress is inadequate, uneven
and inequitable
• New opportunities: medicines,
technologies and approaches
• New era of advocacy for viral
hepatitis
• World Health Assembly requested (May 2014)
• Feasi ility of a d strategies eeded for the eli i atio of hepatitis B a d hepatitis C ith a ie to pote tially setti g glo al targets
• Added HCV in Sustainable Development Goals
• E d the epide i s of AIDS, TB, alaria a d .. a d o at hepatitis, water- or e diseases a d other o u i a le diseases
• Hepatitis alongside HIV, TB & Malaria
• Growing movement around hepatitis
• Treat e t re olutio ; ou try o e tu ; patie t de a d
May 2016: The 69th WHO General Assembly launched/endorsed first Global Health Sector Strategy for Viral Hepatitis Elimination
WHO: Glo al all for HCV eli i atio
May 2016: The 69th WHO General Assembly endorsed/launched first Global Health Sector Strategy for Viral Hepatitis Elimination
VISION
A world where viral hepatitis transmission is stopped and
everyone living with HCV has access to safe, affordable,
and effective prevention, care and treatment services
DEFINITE
GOAL HCV elimination as a major public health threat by 2030
2030 GLOBAL
TARGETS for care
and management
- Reduction in new infections & liver-related mortality
- Increase in diagnosis and enhancing therapy in patients
with HCV by 2030
FRAMEWORKS
FOR ACTION
Universal health coverage, continuum of services (from
screening to diagnosis, therapy & chronic care) and a public
health approach
OMS a definit 5 interventii strategice pentru eliminarea VHB
& VHC ca amenintari globale pana in 2030
http://www.who.int/hepatitis/publications/hep-elimination-by-2030-brief/en/
Distributia infectiei HCV in EU: Prevalenta viremica estimata si numarul total al persoanelor
infectate/tara/2015
The Europea U io HCV Colla orators* Ho ie Razavi….Lia a Gheorghe, Adria Goldis, et al. Hepatitis C virus prevale e a d level of intervention
required to achieve the WHO targets for elimination in the Europena Union by 2030: A modelling study. Lancet Gastroenterol Hepatol 2017. Published on
line March 14, 2017 http://dx.doi.org/10.1016/S2468-1253(17)30045-6
Cascada managementului infectiei C in EU (2015)
Numarul annual al pacientilor tratati inEU 2004-2015
36.4%
4.6% 4.1% 89%
Nou diagnosticati
7.5% anual
0.64%
The Europea U io HCV Colla orators* Ho ie Razavi….Lia a Gheorghe, Adria Goldis, et al. Hepatitis C virus prevale e a d level of intervention
required to achieve the WHO targets for elimination in the Europena Union by 2030: A modelling study. Lancet Gastroenterol Hepatol 2017. Published on
line March 14, 2017 http://dx.doi.org/10.1016/S2468-1253(17)30045-6
Prevalenta viremica, rata de diagnostic si tratament in Eu
in 2015
41.2%
2.4%
The Europea U io HCV Colla orators* Ho ie Razavi….Lia a Gheorghe, Adria Goldis, et al. Hepatitis C virus prevale e a d level of intervention
required to achieve the WHO targets for elimination in the Europena Union by 2030: A modelling study. Lancet Gastroenterol Hepatol 2017. Published on
line March 14, 2017 http://dx.doi.org/10.1016/S2468-1253(17)30045-6
• In 2014 am inceput colaborarea cu CDA (Homie Razavi, Amanda Sibley,
Jessie Gunter, Adrian Goldis) cu scopul de a proiecta pe termen lung
consecintele infectiei VHC (si VHB) in Romania in cateva scenarii : de la
taking no action pana la cresterea diagnosticului, variate scenarii de acces
la Tx antivirala si variate regimuri/eficacitate terapeutica
• CDA (Center for Disease Analysis) este o companie publica de cercetare in
sanatate cu expertiza in epidemiologie si modelare a bolilor
• Este reputata pentru cercetarea si publicatiile in domeniul infectiei VHC
• Metodologie: o abordare multi-disciplinara, cercetare epidemiologica,
studii avansate de modelare, analiza decizionala _ in colaborare cu experti
care furnizeaza datele locale necesare de cea mai buna calitate
Distributia prevalentei si genotipurilor
• Prevalence – CDA estimate based on data from 2010* • Source: Nationwide study, n = 13,460;
– Anti-HCV prevalence
– Viremic Rate – 85% (expert input during Meeting 2)
– Genotype distribution
* Gheorghe L, Iacob S, Csiki E, et al. Prevalence of hepatitis C in Romania: different from European rates? J Hepatol 2008; 49:658
* Gheorghe L, Csiki IE, Iacob S, Gheorghe C, Smira G, Regep L. The prevalence and risk factors of hepatitis C virus infection in adult population in
Romania: a nationwide survey 2006-2008. J Gastrointestin Liver Dis 2010; 19: 373-9;
G1a G1b G1 Total G2 G3 G4 G5 G6
5.4% 92.6% 98.0% 0% 0.8% 1.2%
** Sultana C, Oprisan G, Szmal C, et al. Molecular epidemiology of hepatitis C virus strains from Romania. J Gastrointestin Liver Dis 2011; 20: 261-6.
Year of estimate anti-HCV Prevalence Total Cases
2008 – adults (18-69) 3.2% 529,000
2008 – all ages 3.3% (2.9% - 3.6%) 693,000 (637,000 – 800,000)
Year of estimate Viremic Prevalence Total Cases
2008 – all ages 2.7% (2.5% - 3.1%) 589,000 (541,000 – 680,000)
2016 (projected) – all ages 2.4% (1.9% - 2.7%) 523,000 (418,000 – 571,000)
Distributia prevalentei in raport cu varsta si sexul
0.0%
1.0%
2.0%
3.0%
4.0%
5.0%
6.0%
7.0%
8.0%
9.0%
Report
ed P
revale
nce
HCV Prevalence by Age and Sex — Romania, 2008
Male Female
-
10,000
20,000
30,000
40,000
50,000
60,000
Vir
em
ic C
ases
HCV Infected Population by Age Group — Romania, 2016
As prevalence resulted from studies was not available for all ages, a methodology was used to
extrapolate HCV prevalence for older and younger age cohorts:
- for older people (>74) the same prevalence as in the oldest available population was assumed
- for younger age groups (<18 years old), an exponential decline in prevalence (by 25% in each age
group) was used
* Gheorghe L, Iacob S, Csiki E, et al. Prevalence of hepatitis C in Romania: different from European rates? J Hepatol 2008; 49:658
* Gheorghe L, Csiki IE, Iacob S, Gheorghe C, Smira G, Regep L. The prevalence and risk factors of hepatitis C virus infection in adult population in
Romania: a nationwide survey 2006-2008. J Gastrointestin Liver Dis 2010; 19: 373-9;
Born 1945-1970
Populational
screening?
Incidence a fost calculata pe baza prevalentei si prin
estimare raportata la tarile din jur
In 2008, there were ~19,000 cases (calculation from European CDC data)
We estimate 10,400 new cases in 2017
-
5,000
10,000
15,000
20,000
25,000
30,000
35,000
40,000 N
ew In
fect
ions
New HCV Infections — Romania, 1950-2016
Subiecti diagnosticati
• Anterior – aprox. 90,000 pacienti viremici dg pana in 2014
– Estimarea expertilor pe baza datelor CNAS & date din diverse publicatii
locale
• Nou diagnosticati – 7,500 cazuri viremice anual
– Estimarea expertilor & date de morbi-mortalitate din rapoartele
Institutului National de Statistica si Instiutului National de Sanatate
Publica
Pacienti tratati
• Pacienti tratati 2002 to 2009* - publicatii
• Numarul initierilor terapeutice 2012-2014 (Raportul Comisiei de Experti a
CNAS)
• 2010-2011 estimare pe baza datelor expertilor
• 2015/2016 : inregistrarea centralizata a CNAS
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
1813 2189 3701 3149 2816 2446 4503 4701 5257 5812 6368 6086 4071 3378
8131
5750
DAAs
2381
IFN
based
* Gheorghe L, Pascu O, Ceausu E, Csiki IE, Iacob S, Caruntu F, Simionov I, Vadan R. Access to Peginterferon plus Ribavirin Therapy for Hepatitis C in
Romania between 2002-2009. J Gastrointestin Liver Dis 2012; 19: 161-7167; Gheorghe L, Oral Presentation, EASL 2011, Barcelona
2016
DAA: 5750
(1.05%)
IFNb: 2381
DAA: 5721
(1.046%)
IFNb: 1071
99.5%
1,48% 1,24%
Date epidemiologice specifice/tara in EU 2015:
Ratele de diagnosis si tratament in era DAA
The European Union HCV Collaborators* (Liana Gheorghe, Adrian Goldis). Hepatitis C virus prevalence and level of intervention required to achieve the
WHO targets for elimination in the Europena Union by 2030: A modelling study. Lancet Gastroenterol Hepatol 2017. Published on line March 14, 2017
http://dx.doi.org/10.1016/S2468-1253(17)30045-6
Proceduri de transplant hepatic
• Liver Transplants –
– Romania National Transplant Agency (2005-2015)
http://www.transplant.ro/Statistica.htm
– International Registry on Organ Donation and Transplantation (2000-
2004)
– 27% attributable to HCV based on analysis of data*
Romania National Transplant Agency. 2014. Statistics and data (2005-2013). Available at: http://www.transplant.ro/Statistica.htm
-IRODaT. International Registry on Organ Donation and Transplantation (2000-2004) Available from: URL: http://www.irodat.org
Popes u I, Io es u M, Braso ea u V, … Gheorghe L, et al. - Liver transplantation in Romania - Retrospective analysis of 300 cases. Annals
of Fundeni Hospital 2011; 16: 59-67.
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
7 16 14 12 16 11 20 31 43 32 51 65 75 122 122 96 179
Putem articula o strategie prin care sa trecem de la eradicarea
individuala la eliminarea globala a VHC in Romania
Avem instrumentele (regimuri terapeutice inovatoare) …
Ce se intampla daca nu facem nimic?
Trebuie sa ne focalizam asupra pacientilor cu boala hepatica
avansata/ciroza?
Trebuie sa tratam toti pacientii infectati pentru a atinge tinta
globala OMS de a elimina infectia VHC pana in 2030?
Razavi et al., J of Viral Hepatitis 2014 Razavi H, et al. J Viral Hepat 2014;21(Suppl. 1):34–59.
Germany France
Spain England
Ce se intampla daca nu facem nimic? Consecintele tardive ale infectiei VHC vor creste substantial de-a lungul timpului cu
variate vertex-uri in functie de varsta epidemiei locale
In Romania, pana in 2030, numarul cazurilor viremice VHC va scadea cu 20%,
in timp ce cazurile de HCC, ciroza (de)compensata si mortalitatea hepatica vor
creste cu 25%, 30% si 30%, respectiv
-
100,000
200,000
300,000
400,000
500,000
600,000
Total Infected Cases (Viremic) - Romania
Base
-
500
1,000
1,500
2,000
2,500
3,000
3,500
Liver related Deaths - Romania
Base
-
500
1,000
1,500
2,000
2,500
3,000
3,500
HCC - Romania
Base
-
1,000
2,000
3,000
4,000
5,000
6,000
7,000
Decompensated Cirrhosis - Romania
Base
1900
2400
Crestere cu 25% Crestere cu 30%
2700
3400
Crestere cu 30%
6500 62,900
7500
66,700
Si ley A, Ha KH, A oura hed A, … Gheorghe L, et al. The prese t a d future disease urde of hepatitis C irus i fe tio s ith today’s treat e t paradig . J Viral Hepat 2015; 22 (Dec) (Suppl 4):21-41. doi: 10.1111/jvh.12476
Scadere cu 20%
Scenariul de baza 2017 • 2017
– 10,000 pacienti cu F2 cu co-morbiditati asociate infectiei VHC, F3 si F4 si
2,000 pacienti cu ciroza decompensata si transplant hepatic vor fi tratati cu
DAAs in 2017
2015 2016 2017 2018 2019 2020
Treated 3,400 8,100 12,000 12,000 12,000 12,000
Newly Diagnosed 7,500 7,500 7,500 7,500 7,500 7,500
Fibrosis Stage >= F3 >= F3 >= F2 >= F2 >= F2 >= F2
Treated Age 15-74 15-74 15-74 15-74 15-74 15-74
SVR 69% 90% 95% 95% 95% 95%
Pana in 2030, numarul total de infectii VHC va scadea cu 30%
Decesele de cauza hepatica, HCC & ciroza vor scadea cu 35-40%
-
100,000
200,000
300,000
400,000
500,000
600,000
Total Infected Cases (Viremic) — Romania
Base 2016 Base 2017
-
1,000
2,000
3,000
4,000
5,000
6,000
Decompensated Cirrhosis — Romania
Base 2016 Base 2017
-
500
1,000
1,500
2,000
2,500
3,000
HCC — Romania
Base 2016 Base 2017
-
500
1,000
1,500
2,000
2,500
3,000
Liver Related Deaths — Romania
Base 2016 Base 2017
Scadere cu 40% Scadere cu 30%
Scadere cu 35% Scadere cu 40%
Focus pe F4, F3 & F2 (limitat la F2 plus co-morbiditati corelate VHC)
12,000 – 2017 based scenario
Reducerea rapida a mortalitatii
DAR
Insuficient pentru a atinge tintele OMS
Inutilitatea testarii & depistarii – in absenta accesului la terapie
Cum putem motiva non-interventia?
Nu sunt suficient de bolnav?
Trebuie sa astept sa devin cirotic sau sa apara alte
complicatii/co-morbiditati care sa complice situatia mea?
Pacientii cu ciroza raman la risc pentru HCC si complicatiile HTPo–
ei raman in supraveghere cronica – cei mai s u pi di pu t de
vedere al sistemului de sanatate
Care este nivelul de interventie necesar pentru a atinge
tintele globale ale OMS pana in 2030 ?
• Fara a diagnostica mai multi pacienti si fara a extinde accesul la tratament la
pacientii ˂F2, pool-ul pacientilor eligibili va fi epuizat in 2021
• 2 scenarii au fost evaluate
– Mentinerea scenariului 2017: Toate asumptiile raman constante intre 2017-2030
– Indeplinirea tintelor OMS prin intensificarea diagnosticului si tratamentul tuturor
celor infectati (≥F0) incepand cu 2018
WHO Targets scenario
• Indeplinirea tintelor OMS in Romania necesita:
– Scaling up treatment to 32,000 patients annually by 2025
– Scaling up diagnosis of new patients to 33,000 annually by 2025
– Treating all fibrosis stages starting in 2018
– High level of treatment efficiency
– Efforts to reduce the number of new infections through harm reduction and
treatment as prevention
2015 2016 2017 2018 2020 2025-2030
Treated 3,400 8,100 12,000 15,000 25,000 32,000
Newly Diagnosed 7,500 7,500 10,000 22,000 25,000 33,000
Fibrosis Stage >= F3 >= F3 >= F2 >= F0 >= F0 >= F0
Treated Age 15-74 15-74 15-74 15-74 15-74 15-74
SVR 69% 89% 95% 95% 95% 95%
Indeplinirea tintelor OMS va determina cu 85% mai putine
infectii viremice pana in 2030, vor fi mai putin cu 65% HCC si
ciroza decompensate comparativ cu scenariul 2017
-
100,000
200,000
300,000
400,000
500,000
600,000
Total Infected Cases (Viremic)
Base 2017 WHO Targets
-
500
1,000
1,500
2,000
2,500
3,000
3,500
4,000
4,500
5,000
Decompensated Cirrhosis
Base 2017 WHO Targets
-
500
1,000
1,500
2,000
2,500
HCC
Base 2017 WHO Targets
-
500
1,000
1,500
2,000
2,500
Liver Related Deaths
Base 2017 WHO Targets
Scadere cu 85%
Scadere cu 65%
National Action Plan: 5 strategic directions
1. Un plan national evidence-based
• National Action Plan & structura de guvernare
• Campanii de constientizare & strategie de comunicare
2. Optimizare a interventiilor
• Preventie
• Testare & diagnostic (grupuri cu risc crescut & birth cohort screening )
• Link to care & intensificarea terapiei (acces universal, nivelul terapiei)
3. Abordare : o problema de sanatate publica
• Optimizarea serviciilor & asigurarea unui continuum
• Acces universal & echitabil
• Asigurarea fortei medicale necesare
4. Alocarea suficienta de fonduri si resurse
5. Aplicarea inovatiei de-a lungul intregului continuum - preventie, diagnostic,
tratament