HCV Elimination Mini Policy Summit «Eliminating HCV in Romania» European Parliament, 27 September 2017 How France is eliminating HCV and the role of screening strategies Sylvie Deuffic-Burban, Inserm, Paris & Lille, France
2 Targets and means for HCV elimination Eliminating current chronic HCV infections Decreasing morbidity and mortality related to HCV Eliminating new HCV infections Increasing screening and access to treatment Preventing HCV transmission and reinfection
3 French fight for HCV elimination Two reports of recommendations Management of patients with hepatitis B or hepatitis C virus infection (2014) Therapeutic management and follow-up of people infected with hepatitis C virus (2016)
4 Great heterogeneity across countries Estimated chronic HCV prevalence, diagnosis rate and treatment rate in 2013 (Fig.2 in Dore et al, J Hepatol 2014)
5 Great heterogeneity across countries What is the magnitude of the effects of such differences on morbidity and mortality related to HCV? Estimated chronic HCV prevalence, diagnosis rate and treatment rate in 2013 (Fig.2 in Dore et al, J Hepatol 2014)
6 Modeling study for 6 European countries Reconstruct past incidence of HCV infection (country-specific back-calculation) Simulate progression of HCV disease (state-transition Markov model) Estimate HCV-related morbidity and mortality (HCV-related cirrhosis and deaths) Assess impact of therapy (current treatment practices + reinforcement in diagnosis and treatment rates) Deuffic-Burban et al, Gastroenterology 2012
7 Reduction in 2012-2021 HCV-related mortality vs. no treatment 30% Pegylated bitherapy and triple therapy for GT1 25% Pegylated bitherapy and triple therapy for GT1 + reinforcement of screenig and treatment access 20% 15% 10% 5% 0% Belgium France Germany Italy Spain UK Deuffic-Burban et al, Gastroenterology 2012
8 Reduction in 2012-2021 HCV-related mortality vs. no treatment 30% Pegylated bitherapy and triple therapy for GT1 25% Pegylated bitherapy and triple therapy for GT1 + reinforcement of screenig and treatment access 20% 15% 10% 5% 0% Belgium France Germany Italy Spain UK Deuffic-Burban et al, Gastroenterology 2012
9 Reduction in 2012-2021 HCV-related mortality vs. no treatment 30% Pegylated bitherapy and triple therapy for GT1 25% Pegylated bitherapy and triple therapy for GT1 + reinforcement of screenig and treatment access 20% 15% 10% A combination of enhanced treatment efficacy and improved treatment uptake is required to impact significantly HCVrelated mortality 5% 0% Belgium France Germany Italy Spain UK Deuffic-Burban et al, Gastroenterology 2012
10 Key obstacles to scale-up treatment access (1) High cost of therapy New therapies are expensive whereas available resources are limited Recommendation to treat patients with advanced fibrosis or cirrhosis as a priority
ICER ( per QALY) 11 Cost-effectiveness of treat-all strategies 450000 400000 350000 300000 250000 200000 150000 100000 50000 0 395000 264500 WTP-threshold 40400 8100 21300 19400 9200 23000 GT1 GT2 GT3 GT4 IFN-based new DAAs regadless of fibrosis IFN-free new DAAs regadless of fibrosis Deuffic-Burban et al, J Viral Hepatitis 2016
ICER, per QALY 12 Cost-effectiveness of treat-all strategies with IFN-free new DAAs 500,000 450,000 400,000 350,000 300,000 250,000 200,000 150,000 100,000 50,000 0 Genotype 1* Genotype 2 Genotype 3 Genotype 4 WTP-threshold Cost reduction of new DAAs Deuffic-Burban et al, J Viral Hepatitis 2016
13 Key obstacles to scale-up treatment access (1) High cost of therapy New therapies are expensive whereas available resources are limited Recommendation to treat patients with advanced fibrosis or cirrhosis as a priority France negotiated a substantial price discount on the price of treatment, and committed itself to treating all patients with chronic hepatitis C with direct-acting antivirals (DAAs)
14 Key obstacles to scale-up treatment access (2) Suboptimal screening Based on risk-factors in most countries High proportion of patients with cirrhosis or hepatocellular carcinoma at the time of HCV diagnosis (12%) Recent analysis showed that men aged 18-60 represented around 50% of the undiagnosed population in 2014 Brouard et al, PLoS One 2015; Pioche et al, BEH 2016
15 COST-EFFECTIVENESS OF SCREENING STRATEGY OF HEPATITIS C IN FRANCE: IT IS TIME TO CHANGE RECOMMENDATIONS Deuffic-Burban S 1,2, Huneau A 1, Verleene A 1, Brouard C 3, Pillonel J 3, Le Strat Y 3, Cossais S 1, Roudot-Thoraval F 4, Canva-Delcambre V 5, Mathurin P 2,5, Dhumeaux D 6, Yazdanpanah Y 1,7 1 Inserm, IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; 2 Univ Lille, Inserm, CHU Lille, U995 LIRIC Lille Inflammation Research International Center, Lille, France; 3 Département des Maladies Infectieuses, Santé Publique France, Saint Maurice, France; 4 Service Santé Publique, Hôpital Henri Mondor, Créteil, France; 5 Service des Maladies de l'appareil Digestif et de la Nutrition, Hôpital Huriez, CHRU Lille, Lille, France; 6 Inserm U955, Hôpital Henri-Mondor, Créteil, France; 7 Service de maladies Infectieuses et tropicales, Hôpital Bichat Claude Bernard, Paris, France 0.25% CHC prevalence after one year Treatment when fibrosis stage F2 Treatment regardless of fibrosis stage 0.20% 0.15% 0.10% 0.05% 0.00% Risk based testing One-time men 18-59 testing One-time all 40-59 testing One-time all 40-80 testing One-time all testing In France, although universal screening is associated with the highest costs, it is the most effective strategy and is cost-effective when treatment is initiated regardless of fibrosis (C/E ratio = 35,300 /QALY gained) («Test and treat») Deuffic-Burban et al, EASL 2017
16 Key obstacles to scale-up treatment access (2) Suboptimal screening Based on risk-factors in most countries High proportion of patients with cirrhosis or hepatocellular carcinoma at the time of HCV diagnosis (12%) Recent analysis showed that men aged 18-60 represented around 50% of the undiagnosed population in 2014 Experts in France proposed to extend screening to: - Men aged 18-60 (2014 recommendations) - All adults (2016 recommendations)
17 Key obstacles to scale-up treatment access (3) On-going transmission and recontamination in high-risk population (MSM, DU, migrants, prisoners) Marginalized population with limited access to HCV testing and treatment Intravenous drug use is the source of most new cases of HCV in France
18 Prevalence at 10 years (%) Scenarios: 1, current cascade of care (reference) 2, improvement of HCV testing 3, improvement of linkage-to-care 4, improvement of testing and LTC 5, improvement of adherence to treatment 6, treatment initiated from F0 7, improvement of the entire cascade of care (combination of scenarios 4, 5 and 6) % change from S1 in the number of HCV complications Cousien et al, Hepatology 2016
19 Prevalence at 10 years (%) Scenarios: 1, current cascade of care (reference) 2, improvement of HCV testing 3, improvement of linkage-to-care 4, improvement of testing and LTC 5, improvement of adherence to treatment 6, treatment initiated from F0 7, improvement of the entire cascade of care (combination of scenarios 4, 5 and 6) Cousien et al, Hepatology 2016
20 Scenarios: 1, current cascade of care (reference) 2, improvement of HCV testing 3, improvement of linkage-to-care 4, improvement of testing and LTC 5, improvement of adherence to treatment 6, treatment initiated from F0 7, improvement of the entire cascade of care (combination of scenarios 4, 5 and 6) % change from S1 in the number of HCV complications Cousien et al, Hepatology 2016
21 Prevalence at 10 years (%) Scenarios: 1, current cascade of care (reference) Only 2, improvement a combination of HCV testing of 3, improvement of linkage-to-care 4, improvement of testing and LTC 5, improvement of adherence to early treatment initiation allowed treatment for 6, treatment a substantial initiateddecrease from F0 in both HCV 7, improvement transmission of the and entiremorbidity cascade of care (combination of scenarios 4, 5 and 6) improvements in testing, linkage to care, adherence to treatment and % change from S1 in the number of HCV complications Cousien et al, Hepatology 2016
22 Key obstacles to scale-up treatment access (3) On-going transmission and recontamination in high-risk population (MSM, PWID, migrants, prisoners) Marginalized population with limited access to HCV testing and treatment Intravenous drug use is the source of most new cases of HCV in France Experts in France recommend to - Organize rapid diagnostic tests to promote testing in populations that do not consult traditional healthcare facilities - Favor harm-reduction and care programs rather than legal control and repression of drug use - Promote early treatment of drug users
23 Conclusion To achieve HCV elimination, it is important to Set up a national seroprevalence survey to assess the national HCV burden and assist with the development of a national plan Develop a comprehensive elimination plan that addresses surveillance (including provider training), prevention (e.g., infection control, blood safety, and harm reduction), testing (including public awareness campaigns and improving implementation of screening activities), linkage to care and treatment access Develop mathematical models to evaluate public health strategies
24 Inserm Team "Decision Sciences in Infectious Disease Prevention, Control and Care And clinicians from Inserm LIRIC and CHRU at Lille