Setting the Stage Key Challenges in Elimination Jordan J. Feld MD MPH Toronto Centre for Liver Disease Sandra Rotman Centre for Global Health University of Toronto
Disclosures Consulting: Abbvie, Contravir, Gilead, Janssen, Medimmune, Merck Research: Abbvie, Gilead, Janssen, Merck Speaking: None
WHO takes the lead We know the goal Growing momentum some challenges along the way
Major gaps to overcome Testing Gap Treatment Gap
Challenges to overcome Data quality/quantity The Care Continuum Screening & Diagnosis Linkage to care Treatment Before the Cascade Political will & finances
Global burden Polaris Observatory excellent resource global, regional and country-level data 175M 71M Major drop in estimate Better analysis Viremia not Ab + Correct age distribution?better data Polaris Observatory
High quality data critical Prevalence (Viremic) 10% of 659 healthy patients 0.7% of 659 healthy patients Population = 120M 1.2 vs 12M people! Data inform everything else: Burden (competing priorities) Strategy screening, linkage, treatment everything! Important to acknowledge what we don t know Gower J Hep 2014, Alamayehu BMC Res Notes 2011, Abate Ethiop J Health Sci 2016
What about in Canada? Considered to have high quality data but Prevalence data lacking Modeled estimates Back calculation method use incidence of HCV-related HCC to estimate previous cases of HCV predicted 0.64% (220,697 people) Workbook method multiply prevalence in risk group by number of people in that risk group e.g. PWID 0.71% (245,987 people)
Positive (%) Objective data Residual serum from commercial lab tested for HCV Ab in 10,000 Ontarians born 1945-75 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Prevalence of 1.55%, highest men 1960-64 (3.0%) 1945-1949 1950-1954 1955-1959 1960-1964 1965-1969 1970-1975 Males % Females % Year-Band of birth Extrapolated to Canadian population: 362,129 HCV Ab+ve and 267,975 RNA +ve much higher than models! Bolotin In Press PLoS One
Data a major challenge Countries need to prioritize high quality data Needs continual updating particularly as move toward elimination Need to acknowledge where data are lacking POLARIS data as Green high quality links to the data with methodology Yellow intermediate quality Red low quality Sometimes a bit of public shaming can be helpful
Challenges to overcome Data quality/quantity The Care Continuum Screening & Diagnosis Linkage to care Treatment Before the Cascade Prevention Political will & finances
We need more than great drugs Curing the individual is now easy Curing the population will take a lot more work SVR in individuals SVR in the population Thomas Nature Medicine 2012
The cascade of care not just Tx Modeled data for non-va US population Diagnosis Access Treated SVR Yehia PLoS One 2014 But won t this all get better with IFN-free therapy?
Percentage An elimination strategy Reminder in EPR 92,012 visits 16,772 (18%) tested 715 Ab + (4.2%) 68% Left side of the cascade 80% actually more important 57% 90% DAAs only help here 90% (46% RNA+) Anti-HCV Positive N=715 RNA Tested N=488 RNA Positive N=388 Initiated Treatment N=223 Completed Treatment N=201 Achieved SVR N=180 Even with effective treatment, major gaps in cascade of care! Mera MMWR 2016
Too much focus on therapy & access not enough on screening Countries risk running out of hepatitis C patients to treat, says World Hepatitis Alliance To reach elimination targets: Diagnosis: 1.5 M in 2016 4.5 M new diagnoses per year Treatment: 1.76 M in 2016 5 M per year H. Razavi World Hepatitis Summit, Sao Paulo Brazil 2017
The first few years are easy % of chronic HCV 2015 2016 16 14 12 We treat those who are diagnosed and in care 10 8 6 4 2 0 Canada China Egypt France Georgia Germany Italy Portugal Spain UK US Australia CDA 2017: Polaris Observatory (http://centerforda.com/polaris/)
New Diagnoses per year Treatment per year Tough even for the leaders Australia Numbers the same Much harder in 2025 than 2018 Will need very active case-finding All steps in continuum likely harder with time Harder to find, Harder to engage, Harder to cure (?) Polaris Observatory
Diagnosis needs simplification Step 1 See the doctor Step 2 To the lab for HCV Ab Step 3 See the doctor for result Step 4 To the lab for HCV RNA Loss to F/U Loss to F/U Loss to F/U Step 5 See the doctor for result Loss to F/U Loss to F/U Step 6 Start DAA therapy (may be additional steps: fibrosis assessment, approvals etc) Lots of places to get lost particularly if HCV not a priority
Improving diagnostics Point-of-care PCR test Saliva or blood rapid antibody test Dried Blood Spot Some improvements but variable quality (few WHO pre-qualified) Very variable cost sometimes more than therapy!
A preferred paradigm Diagnosis & linkage to care combined into a single visit Grebely.Feld Exp Rev Mol Diag 2017
Challenges to overcome Data quality/quantity The Care Continuum Screening & Diagnosis Linkage to care Treatment Before the Cascade Prevention Political will & finances
Barriers to access Fibrosis Drug / Alcohol Use No scientific basis for either form of restriction Inadequate access to non-invasive testing Improving with time but many countries continue to have barriers Barua Ann Int Med 2015
Treatment in primary care Randomized to receive care from primary care practitioner vs specialist Nurse Practitioner Treatment equally or more effective by nurse or family doctor than specialist Kattakhuzy Annals Int Med 2017 Primary Care Physician Specialist Total
Australia leading the way Gastro ID Other specialist GP Other 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% March April May June July August September October November December Dore G - Kirby Institute 2017 (http://kirby.unsw.edu.au/researchprograms/vhcrp-newsletters)
Challenges to overcome Data quality/quantity The Care Continuum Screening & Diagnosis Linkage to care Treatment Before the Cascade Prevention Political will & finances
Upstream of the cascade At risk for HCV Prevention Strategies Diagnosis Access Treated SVR Yehia PLoS One 2014 Prevention strategies critical
Prevention Low & Middle Income Countries Reduce injection use Injection safety Blood safety Harm reduction for PWID (Treatment to reduce prevalence) High income countries Harm reduction for PWID (NSP, OST, SIS) Everywhere: Vaccine research
Projections for 2017 1.6 million new HCV infections Worldwide, 68.5 million HCV infected in 2017 (-1.8%) 1.5 million cures 350,000 HCV related deaths 1.04 million non-hcv related deaths Despite massive treatment uptake very limited overall effect Only 9 countries on target to meet 2030 elimination targets Courtesy of Andrew Hill, World Hepatitis Summit 2017
Challenges to overcome Data quality/quantity The Care Continuum Screening & Diagnosis Linkage to care Treatment Before the Cascade Prevention Political will & finances
- 900 delegates - Policy makers - Ministers of Health - WHO, NGOs - Clinicians - Community members
Needs to be followed with concrete action National Action Plans/Strategies - Clear plan to meet WHO elimination goals - Address full continuum: - Prevention - Screening/Diagnosis - Linkage to care - Treatment - Prevention - Continued data collection to measure progress
Summary Elimination is a tall order Lots of challenges along the way But don t despair We have the tools We are about to hear some success stories and strategies to overcome the challenges We need better evidence to know the way forward
Parallel Streams Clinical Basic Science Public Health HCC Symposium Viral Hepatitis in Indigenous Populations NoHep Village - WHA
Net Cure Net Cure How are we doing? Net cure = SVR + HCV deaths new infections ie net loss in HCV +ve 35% Countries with decreasing HCV prevalence 26% 15% 12% 9% 8% 7% 7% 5% 5% -5.6% -3.4% -3.3% -3.2% -3.1% -2.7% -2.7% -2.5% -2.3% -4.6% Countries with increasing HCV prevalence Hill J Vir Eradication 2017
Net Cure And regionally/globally? 7.0% 5.9% 3.6% 1.2% 0.2% 0.4% -2.1% -1.2% -4.3% North America North Africa/ MidEast Europe, Western Latin Asia & America Pacific Sub- Saharan Africa Europe, Central East Missing Global countries Some progress but clearly a lot of work to do! Hill J Vir Eradication 2017