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 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 2016-2021 draft Global Health Sector Strategy on Viral Hepatitis, Gottfried Hirnschall, Director of the WHO Department of HIV and Global Hepatitis Program
WHO: Glo al all for HCV eli i atio VISION DEFINITE GOAL 2030 GLOBAL TARGETS for care and management FRAMEWORKS FOR ACTION 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 HCV elimination as a major public health threat by 2030 - Reduction in new infections & liver-related mortality - Increase in diagnosis and enhancing therapy in patients with HCV by 2030 Universal health coverage, continuum of services (from screening to diagnosis, therapy & chronic care) and a public health approach May 2016: The 69th WHO General Assembly endorsed/launched first Global Health Sector Strategy for Viral Hepatitis Elimination
Care sunt tintele de impact ale strategiei de eliminare a HCV & HBV pana in 2030?
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/
Magnitudinea infectiei VHC in EU & Romania
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 Nou diagnosticati 7.5% anual 89% 4.6% 0.64% 4.1% 36.4% 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
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
Evidence-based data & date asumate pentru Romania (inputs & assumptions)
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 Year of estimate 2008 adults (18-69) anti-hcv Prevalence 3.2% Total Cases 529,000 2008 all agesrate 85% (expert input 3.3% (2.9% - 3.6%) Viremic during Meeting 2) 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) 2.4% (1.9% - 2.7%) 523,000 (418,000 571,000) Genotype distribution 2016 (projected) all ages G1a G1b G1 Total G2 G3 5.4% 92.6% 98.0% 0% 0.8% G4 G5 G6 1.2% * 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; ** 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.
Distributia prevalentei in raport cu varsta si sexul 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 9.0% 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 0.0% HCV Infected Population by Age Group Romania, 2016 60,000 Viremic Cases Reported Prevalence HCV Prevalence by Age and Sex Romania, 2008 50,000 40,000 Born 1945-1970 Populational screening? 30,000 20,000 10,000 - Male Female * 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;
Incidence a fost calculata pe baza prevalentei si prin estimare raportata la tarile din jur New HCV Infections Romania, 1950-2016 40,000 New Infections 35,000 30,000 25,000 20,000 15,000 10,000 5,000 - In 2008, there were ~19,000 cases (calculation from European CDC data) We estimate 10,400 new cases in 2017
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 1813 2003 2189 2004 3701 2005 3149 2006 2816 2007 2446 2008 4503 2009 4701 2010 5257 2011 5812 2012 6368 2013 6086 2014 4071 2015 2016 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
Date epidemiologice specifice/tara in EU 2015: Ratele de diagnosis si tratament in era DAA 2016 99.5% DAA: 5750 (1.05%) IFNb: 2381 1,48% DAA: 5721 (1.046%) IFNb: 1071 1,24% 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 (20002004) 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 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. 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?
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 Germany France Spain England Razavi H, et al. J Viral Hepat 2014;21(Suppl.Razavi 1):34 59. et al., J of Viral Hepatitis 2014
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 Total Infected Cases (Viremic) - Romania Liver related Deaths - Romania 3,500 600,000 500,000 2,500 400,000 2,000 300,000 2700 1,500 200,000 100,000 3400 3,000 1,000 Scadere cu 20% 500 Crestere cu 30% - - Base Base HCC - Romania 3,000 2,500 2,000 Decompensated Cirrhosis - Romania 2400 3,500 6,000 66,700 5,000 1900 4,000 1,500 3,000 1,000 2,000 500 7500 7,000 Crestere cu 25% 1,000-6500 62,900 Crestere cu 30% - Base Base 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
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% Total Infected Cases (Viremic) Romania Decompensated Cirrhosis Romania 600,000 6,000 500,000 5,000 400,000 4,000 300,000 3,000 200,000 2,000 Scadere cu 30% 100,000 1,000 - - Base 2016 Base 2017 Base 2016 HCC Romania 3,000 2,500 2,500 2,000 2,000 1,500 1,500 500 1,000 Scadere cu 40% Base 2017 Liver Related Deaths Romania 3,000 1,000 Scadere cu 40% Scadere cu 35% 500 - - Base 2016 Base 2017 Base 2016 Base 2017
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 Total Infected Cases (Viremic) Decompensated Cirrhosis 5,000 4,500 4,000 3,500 3,000 2,500 2,000 1,500 1,000 500-600,000 500,000 400,000 Scadere cu 85% 300,000 200,000 100,000 - Base 2017 WHO Targets Base 2017 HCC Liver Related Deaths 2,500 2,500 2,000 2,000 1,500 1,500 1,000 1,000 500 500 - - Base 2017 WHO Targets WHO Targets Scadere cu 65% Base 2017 WHO Targets
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
It s ti e for a tio Let s start ow!