Available Hepatitis Information: how can this be used to convince decision makers and potential funders H. Razavi June 6, 2015 Viral Hepatitis Prevention Board Meeting, London, UK 56 June 2015
It s not what we don t know that gives us trouble, it s what we know that ain t so Will Rogers
What is it that we know that ain t so: The total number of HCV infections, diagnosis rate and treatment rate is unknown. Development of a national strategy requires perfect information e.g., a robust nationwide surveillance study. The epidemiology data in developing countries is less robust than Western Europe and US. There are not enough healthcare providers to increase treatment. What we have learned from HIV can be directly applied to HCV. 3
German national survey vs notification data 3.00% 2.50% 2.00% 1.50% 1.00% Male Female DEGS1 (n= 7,047 in adults 1879) (PoethkoMuller 2013) 0.50% 0.00% 4 0 4 5 9 10 14 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75 79 80 84 85+ 1.80% 1.60% 1.40% 1.20% 1.00% 0.80% 0.60% Male Female RKI notifications 2012 (n= 4,971) 0.40% 0.20% 0.00% 0 4 5 9 10 14 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75 79 80 84 85+
AntiHCV Prevalence 88 countries have reported antihcv prevalence (88% of world s adult population and 85% of infections) Data Quality Gower, E., Estes C., Hindman, S., RazaviShearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014. 5
There are 80 (62103) million viremic infections worldwide corresponding to a prevalence of 1.1% (0.91.4%) Prevalence (Viremic) 0.0%0.6% 0.6%0.8% 0.8%1.3% 1.3%2.9% 2.9%7.8% Total Infected (Viremic) 0200K 200K650K 650K1.9M 1.9M3.5M 3.5M9.2M Gower, E., Estes C., Hindman, S., RazaviShearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014. 6
Genotype data is available for 99 countries North America Europe, Western Europe, Central Europe, Eastern Asia, Central Asia Pacific, High Income Asia, South Caribbean Asia, Southeast Latin America, Central Asia, East Latin America, Tropical Prevalence (Viremic) Total Infected (Viremic) 0200K Australasia 200K650K 650K1.9M 1.9M3.5M 3.5M9.2M Latin America, Southern Latin America, Andean North Africa/Middle East SubS Africa, Central SubS Africa, Southern SubSaharan Africa, West Gower, E., Estes C., Hindman, S., RazaviShearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014. 7
HCV Prevalence and Genotype Distribution Africa & Middle East Morocco Algeria Tunisia Libya Egypt Palestine Israel Lebanon Syria Jordan Kuwait Iraq Guinea Bissau Gambia UAE Saudi Arabia Iran Burkina Faso Ghana Central African Republic Ethiopia Congo Nigeria Equatorial Guinea Mozambique Madagascar Gabon South Africa Prevalence (Viremic) 0.0%0.6% 0.6%0.8% 0.8%1.3% 1.3%2.9% 2.9%7.8% Total Infected (Viremic) 0200K 200K650K 650K1.9M 1.9M3.5M 3.5M9.2M Gower, E., Estes C., Hindman, S., RazaviShearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014. 8
The present and future HCV disease burden has been modeled for over sixty countries/ regions Argentina European Union Japan Saudi Arabia Australia Finland Latvia Singapore** Austria France Lebanon* Slovakia Belgium Ghana** Lithuania Slovenia Brazil Georgia** Luxembourg South Africa Bulgaria* Germany Malta South Korea Canada Greece Mexico Spain Chile** Hong Kong** Mongolia Sweden China** Hungary Netherlands Switzerland Colombia** Iceland New Zealand Taiwan* Croatia** India Norway Turkey Czech Republic Indonesia* Pakistan UAE* Denmark Iran* Poland United States Egypt Ireland Portugal England Israel Romania Estonia* Italy Russia * Need validations with local experts 9
A systematic process is used to develop consensus estimates of HCV disease burden in each country PreMeeting 1» Conduct an exhaustive literature search for English and nonenglish published studies finding key inputs HCV prevalence, age distribution, genotype, diagnosed, treated, incidence» Prepopulate the disease burden model and send out a slide deck summarizing findings Meeting 1 with local experts (3 hours)» Provide a brief overview of the methodology and model» Review assumptions and identify data gaps» Make modifications to key inputs based on expert input and unpublished data» Identify action items with key responsibilities Between Meetings 1 & 2» Work with stakeholders to gather additional data and recalibrate the model Meeting 2 with local experts (3 hours)» Review updated inputs and gain agreement» Develop strategies to manage the HCV disease & cost burdens over the next 20 years PostMeeting 2» Develop manuscripts to be submitted to peerreviewed journals» Submit abstracts to conferences to present findings 10 10
2011 Treatment rate is available for >50 countries Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014;21 Suppl 1:3459. Hatzakis A, Chulanov V, Gadano AC, Bergin C, BenAri Z, Mossong J, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm J Viral Hepat 2014. Submitted for publication 30 July 2014. 11
Age distribution for >50 countries Percentage of All HCV infections 18% 16% 14% 12% 10% 8% 6% 4% 2% Primary Risk Factor Nosocomial IDU 0% Age Cohort Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014;21 Suppl 1:3459. Hatzakis A, Chulanov V, Gadano AC, Bergin C, BenAri Z, Mossong J, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm J Viral Hepat 2014. Submitted for publication 30 July 2014. 12
Change in disease burden and impact of different strategies France Total Infected Cases (Viremic) France All Cirrhosis France 250,000 200,000 150,000 100,000 50,000 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 Basecase Increased Efficacy Only Increased Efficacy & Treatment Basecase Increased Efficacy Only Increased Efficacy & Treatment Total HCC Cases France Liverrelated Deaths France 2,000 1,800 1,600 1,400 1,200 1,000 800 600 400 200 1,800 1,600 1,400 1,200 1,000 800 600 400 200 Basecase Increased Efficacy Only Increased Efficacy & Treatment Basecase Increased Efficacy Only Increased Efficacy & Treatment Wedemeyer H, Duberg AS, Buti M, Rosenberg WM, Frankova S, Esmat G, et al. Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat 2014 May;21 Suppl 1:6089. 13
Change in disease burden and impact of different strategies Egypt 7,000,000 6,000,000 5,000,000 4,000,000 3,000,000 2,000,000 1,000,000 Total Infected Cases (Viremic) Egypt 900,000 800,000 700,000 600,000 500,000 400,000 300,000 200,000 100,000 All Cirrhosis Egypt Basecase Increased Efficacy Only Increased Efficacy & Treatment Basecase Increased Efficacy Only Increased Efficacy & Treatment 25,000 20,000 15,000 10,000 5,000 Total HCC Cases Egypt 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 Liverrelated Deaths Egypt Basecase Increased Efficacy Only Increased Efficacy & Treatment Basecase Increased Efficacy Only Increased Efficacy & Treatment Wedemeyer H, Duberg AS, Buti M, Rosenberg WM, Frankova S, Esmat G, et al. Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat 2014 May;21 Suppl 1:6089. 14
Change in disease burden and impact of different strategies Russia 7,000,000 6,000,000 5,000,000 4,000,000 3,000,000 2,000,000 1,000,000 Total Infected Cases (Viremic) Russia 500,000 450,000 400,000 350,000 300,000 250,000 200,000 150,000 100,000 50,000 All Cirrhosis Russia Base Case Increased Efficacy Only Increased Efficacy & Treatment Basecase Increased Efficacy Only Increased Efficacy & Treatment 18,000 16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 Total HCC Cases Russia 18,000 16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 Liverrelated Deaths Russia Basecase Increased Efficacy Only Increased Efficacy & Treatment Base Case Increased Efficacy Only Increased Efficacy & Treatment Gane E, Kershenobich D, SeguinDevaux C, Kristian P, Aho I, Dalgard O, et al. Strategies to manage hepatitis C virus (HCV) infection disease burden volume 2. J Viral Hepat 2015 Jan;22 Suppl 1:4673. 15
There is a finite number of HCV cases to be treated Treated Patients France Treated Patients Egypt 25,000 350,000 20,000 15,000 300,000 250,000 200,000 10,000 150,000 5,000 100,000 50,000 Basecase Increase Efficacy & Treatment Basecase Increase Efficacy & Treatment Treated Patients Russia 450,000 400,000 350,000 300,000 250,000 200,000 150,000 100,000 50,000 Basecase Increase Efficacy & Treatment 16
Fold increase in annual treatment rate required to achieve HCV >90% reduction in prevalence by 2030 16 Fold Increase in Tx Rate to Achieve Elimination 14 12 10 8 6 4 2 0 Denmark Ireland Brazil Portugal Slovak Republic Belgium New Zealand Egypt Czech Republic Sweden Switzerland England Austria Germany Poland Norway France Luxembourg Netherlands 0 1 2 3 4 5 6 Annual Treatment Rate (%) at Baseline 17
Cost of screening HCVinfected population by birth cohort for countries with known diagnostic costs Prevalence and diagnosis rates Example: Switzerland Birth Cohort General 4044 years 50% of cases 75% of cases (19242013) (19691973) (19591978) (19491983) AntiHCV prevalence 1.3% 2.3% 2.2% 2.1% HCV RNA prevalence 1.0% 1.8% 1.8% 1.6% Diagnosis Rate 40% 40% 40% 40% Number of tests required to identify 1 viremic case to treat (n) AntiHCV 158 92 94 101 HCV RNA 1.3 1.3 1.3 1.3 Genotype 1 1 1 1 Associated costs to identify 1 viremic case, by test type (CHF) AntiHCV 3,939 2,295 2,357 2,531 HCV RNA 226 226 226 226 Genotype 180 180 180 180 Total 4,345 2,701 2,763 2,937 Bruggmann P, Negro F, Bihl F, Blach S, Lavanchy D, Müllhaupt B, Razavi H, Semela D, Birth Cohort Distribution and Screening of Viremic HCV Infections in Switzerland AASLD/EASL 2014 Special Conference on Hepatitis C, 2014, New York 18
Direct and indirect cost of HCV with and without new treatment Egypt 600,000 500,000 400,000 300,000 2500 2000 1500 Direct Cost 200,000 1000 100,000 0 DALY total by year Current Strategy 500 0 6,000 5,000 2015 2016 2017 Indirect Cost 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 DALY total by year Disease Control Strategy 4,000 Current Therapy Disease Control Strategy Cumulative DALYs 20152030 8.24 Mill 5.8 Mill DALYs Averted vs Current Therapy 2.4 Mill Cumulative Direct Costs 20152030 (US$) 25.5 Bln 20 Bln Incremental cost (US$) 5.5 Bln ICER/DALY averted (US$) 2,290 Cumulative Indirect Costs 20152030 (US$) 67.2 Bln 44.6 Bln Incremental cost (US$) 22.6 Bln ICER/DALY averted (US$) 9,350 Cumulative Total Costs 20152030 (US$) 92.7 Bln 64.6 Bln Incremental cost (US$) 28.1 Bln ICER/DALY averted (US$) 11,650 3,000 2,000 1,000 0 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000 0 2015 2016 2017 2018 Total Cost 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 Estes, et al. Future Economic Burden of Hepatitis C in Egypt: Impact of Treatment Strategies. AASLD/EASL 2014 Special Conference on Hepatitis C, 2014, New York, abstract # 18 19
What is next? A global observatory for HCV, HBV and HDV» Actual epidemiology and disease burden data» Modeling for HBV» Comparison against forecasts» All open access 20