Hepatitis C “Hidden Harm ”

1. Trinity College Dublin Hepatitis C“Hidden Harm” Prof Suzanne Norris Consultant Hepatologist St James’s Hospital

2. Global burden of Hepatitis C virus infection: Europe Cornberg M et al Liver International 2011; 31 (Suppl 2):30-60

3. Global Burden of HCV:Barriers to Testing, Care, Treatment • Developed countries • Most HCV-infected persons are unaware of their infection • Inadequate knowledge and awareness of HCV among healthcare providers and their patients • Cost-related factors • Lack of HCV screening policies • Developing countries • Same barriers as in developed countries, plus • Low political, provider, and community awareness of HCV as a significant health threat • Lack of understanding among public health officials on the true burden of disease • One-third of the WHO Member Countries do not collect prevalence data for viral hepatitis Averhoff FM, et al. Clin Infect Dis. 2012;55(suppl 1):S10-S15.

4. Hepatitis C in Ireland Number of notifications of hepatitis C 2004-2010, by sex and mean age By 2013, 12,365 diagnosed Prevalence is 20,000-50,000

5. Mean annual notification rates per 100,000 for hepatitis C by age and sex, 2004-2012

6. Most likely risk factor (%) for cases of hepatitis C notified 2007-2010 (where data available, n=2772, 50%)

7. Most likely risk factor (%) for cases of hepatitis C notified 2007-2010 (where data available, n=2772, 50%) HCV genotypes 1 and 3 are the most common

8. In Ireland, 62–79% of injection drug users are positive for anti-HCV Prevalence of HCV among injection drug users in Ireland 62–79% Fitzgerald et al. IMJ 2001;170:32 Grogan et al. IMJ 2005;174(2):14 Smyth et al. Addiction 1998;93(11):1649 Smyth et al. J Epid Com Health 2003;57;310 Cullen et al. IMJ 2003;172(3):1213

9. Epidemiology in Ireland: Prisons 17–21% started injecting drugs in prison Department of Community Health and General Practice, Trinity College, Dublin. Hepatitis B, Hepatitis C and HIV In Irish Prisoners, Part II:Prevalence and Risk in Committal Prisoners 1999

10. Epidemiology: Ireland • No seroprevalence data from general population • Of 62,667 women screened in the anti-D RhIg Programme, seroprevalence of HCV Ab positivity was 1.1%Kenny-Walsh et al, NEJM1999;340:1228 • Optional HCV Screening Programme of transfusion recipients, 1995 – 2002: 14,917 individuals screened (85% female) with seroprevalence rate of 0.3% Davoren et al, Transfusion 2002;42:1501

11. HCV and the individual • 10–20% of patients with HCV will develop cirrhosis after 20–30 years EASL. J Hepatol 2014;60:392–42

12. Risk factors that may affect progression of HCV Infection

13. Healthy Liver Hepatic Fibrosis Cirrhosis Liver Cancer

14. Effect of chronic HCV infection on QoL measured using SF36 questionnaire 100 90 Controls 80 SF36 score 70 Mild disease 60 50 40 Severe disease 30 20 10 0 Pain Physical functioning Socialfunctioning Role –physical Role –emotional Mentalhealth Energy andfatigue General healthperception Foster GR et al. Hepatology 1998;27:209–12

15. Change in quality of life following interferon therapy 35 * * Responder (n=41) Non-responder (n=396) 30 25 20 * * 15 Change from baseline inHRQoL(SF-36 scale) * ** 10 5 0 Physical function Role physical Bodily pain General health Social function Role emotional Mental health Vitality –5 * p<0.05 **p<0.01 US multicentre randomised double-blind controlled study of 704 patients receiving 3µg inteferon, 9µg consensus interferon or 15µg interferon-alfa-2b 3 times a week for 24 weeks. Responder =undetectable HCV RNA at 24 weeks’ post-treatment Bonkovsky HL et al. Hepatology 1999;29:264–70

16. Indirect economic costs of HCV 30 Patients with HCV Controls 20 Patients (%) 10 0 Presenteeism Overall work impairment Activity impairment Absenteeism • Data from the 2009 US National Health and Wellness Survey showed patients with HCV were significantly less likely to be employed vs controls (p<0.0001). HCV in the EU population significantly impacts several domains of HRQL(p<0.05)DiBonaventura M et al. J Med Econ 2011;14:253–61DiBonaventura M et al. Eur J Gastroenterol Hepatol 2012;24:869–77

17. REVEAL Study: risk of chronic HCV infection on hepatic and extrahepatic deaths • Community based, long-term, prospective study • Invited 89,293 residents (aged 30-65 years) from 7 townships in Taiwan • 23,820 (26.7%) agreed to participate • Current analysis (n=19,636 HBsAg-negative) • Anti-HCV seronegative (n=18,541) • Anti-HCV seropositive (n=1095) • Detectable HCV RNA: 69.4% • 2394 deaths over 317,742 person-years of follow-up • Average follow-up: 16.2 years • Overall mortality: 753.4 per 100,000 person-years REVEAL: Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer. Enrollment 1991-1992. Last follow-up: 12/2008. Lee M-H, et al. J Infect Dis. 2012; 206:469-477.

18. REVEAL Study Mortality: Liver Cancer and Cirrhosis Chronic Liver Diseases and Cirrhosis (n=76) Liver Cancer (n=115) Anti-HCV+, HCV RNA detectable Anti-HCV+, HCV RNA undetectable Anti-HCV- Anti-HCV+, HCV RNA detectable Anti-HCV+, HCV RNA undetectable Anti-HCV- 10.4%* Cumulative Mortality (%) Cumulative Mortality (%) 2.8%† 1.6% 0.3% 0.3% 0% 0 2 4 6 8 10 12 14 16 18 20 0 2 4 6 8 10 12 14 16 18 20 Follow-Up (Years) Follow-Up (Years) REVEAL: Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer. *P<0.001 for comparison among all 3 groups and P<0.001 for HCV RNA detectable versus undetectable. †P<0.001 for comparison among all 3 groups and P=0.005 for HCV RNA detectable versus undetectable. Lee M-H, et al. J Infect Dis. 2012; 206:469-477.

19. UK hospital admissions due to HCV-related ESLD and HCC are increasing Annual number of individuals in England, Scotland and Wales hospitalised with HCV-related ESLD or HCV-related HCC:1998-2010 HPA report 2012 Available at: www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1317135237627 Accessed June 2013

20. UK deaths from HCV-related ESLD and HCC are increasing Deaths from HCV-related ESLD or HCV-related HCC mentioned on the death certificate in the UK:1996-2010 HPA report 2012 Available at: www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1317135237627 Accessed June 2013

21. Burden of HCC in Ireland

22. HCV-related transplants2001-2011 We apologise that this information is not able to shared online as it is unpublished data

23. A viral cure can be achieved in HCV infection Achievement of a sustained virologic response (SVR) following completion of treatment is indicative of successful therapy and is synonymous with a cure Acute Infection Chronic Infection Successful Therapy Soriano V, et al. J Antimicrob Chemother. 2008;62:1–4. Smith BD, et al. MMWR. 2012;61(4):1-32. Metzner KJ. Future Virol. 2006;1:377-91

24. Does SVR equal cure of liver disease? • Viral eradication stops progression of disease • Mild Disease - long-term outcome = pop’n risk 286 pts with SVR after IFN therapy Follow-up post SVR (n=286) SVRs (n=286) Survival Matched general population Proportion of patients % survival Decompensation/HCC Time [yrs] Time [yrs] Veldt Gut 2002

25. SVR saves lives Long-term follow-up of patients with cirrhosis post-treatment Non-SVR SVR SVR eliminates liver failure Van de Meer et al 2012

26. Benefits of SVR: reduction in liver-related disease Number of events Mortality Rates and Hospital Episode Rates (Per 100 Person Years) by SVR Status Observed Among 1,215 Post-Treatment HCV Patients in Scotland, 1996-2007 Innes HA et al. Hepatology 2011;54:1547-1558.

27. Bottom line Non-Cirrhotics • SVR = cure  normal life expectancy Cirrhotics • SVR eliminates liver failure • SVR greatly reduces the risk of HCC • SVR improves liver-related AND overall survival In a cost curtailed environment is curing a disease more effective than managing a disease - diabetes versus HCV?

28. Case-finding critical Deuffic-Burban et al Gastro 2012 Reduction in cumulative Incidence of death Belgium France Germany Italy Spain UK Treatment only effective for those who receive it…

29. Modelled number of IDUs in Scotland with liver failure with different uptake rates of HCV therapy, 2008-2030 0 former IDUs per year 225 former IDUs per year 1,000 former IDUs per year (up to) 2,000 former IDUs per year Assuming uptake of HCV antiviral therapy by:

30. Number of patients ever treated with PEG per 100 prevalent HCV cases* by country until end of 2005 16 3 1 Lettmeier et al JHepatol 2008

31. HCV mono-infection landscape in Ireland We apologise that this information is not able to shared online as it is unpublished data

32. HCV mono-infection treatment programme in St James’s Hospital We apologise that this information is not able to shared online as it is unpublished data

33. Current Challenges - unmet need We apologise that this information is not able to shared online as it is unpublished data

34. HCV in Ireland: where is it? Three big reservoirs • Current injectors • Ex-injectors • Hidden • Finding them may take a screening campaign (‘baby boomers’) • Immigrants • Pattern of infection unpredictable (‘healthy migrant’ effect) • Access can be difficult • Not everyone wants to be associated with these virus

35. Barriers to HCV Care HCV Infection HCV Infection Patient factors Social support homelessness, social isolation, culture, stigmatisation, language and ethnicity Treatment side-effects Patient fears and impact on quality of life and career Cost Financial concerns around treatment and daily living costs and lack of funding support HCP factors Lack of education Lack of awareness of HCV among primary care staff Lack of screening and referral facilities Lack of communication with specialist services Clinician bias Lack of urgency from the Department of Health and HSE. Diagnosis Diagnosis Referral to Specialist Referral to Specialist

36. What will it take to overcome current barriers? Future: better treatments • Simpler therapy • Shorter duration • More tolerable • Efficacious Opportunity to reduce morbidity, mortality and associated healthcare costs

37. What will it take to overcome current barriers? • Advocacy • Leadership • Political partnership

39. I.C.O.R.N. • Irish Hepatitis C Outcomes Research Network. Established February 2012. • Collaboration between ISG, IDSI, NCPE and HPSC, research networks, and pharma. • The goal of this collaboration is to optimise the quality of care of patients with hepatitis C (HCV) treated with direct-acting antiviral therapy.

40. I.C.O.R.N. • to provide a governance structure and stewardship programme for clinicians and clinical nurse specialists • develop national treatment guidelines • establishment of national treatment HCV registry • platform for HCV clinical trials and HCV related research • R&D models of care to enhance equitable access to services for all assess differing treatment models

41. DAAs – decision to reimburse We apologise that this information is not able to shared online as it is unpublished data

42. Outputs from registry • Real time e-data capture tool developed by ICORN (A O’Leary) in conjunction with DCCR (J. McCourt, R. Gaur) • Real-world, observational data • Effectiveness vs efficacy • Analysis of response modifiers • Quantitative analysis of adverse events • Economic consequences • PROMs and PREMs

43. ICORN HCV Roadmap 2014 • Development of Model of Care - Network of treatment sites • Expansion of Registry • Advocacy for Implementation of National HCV Strategy • Education and awareness • Surveillance and screening • Infrastructural programmatic support to consolidate national programme

44. 36 recommendations across four key areas: • Surveillance • Education & Prevention • Screening • Treatment access & delivery

45. Reality or Fantasy • Will screening be acceptable in primary and care? • Who will pay? • Does infrastructure exist for referral and treatment? • New models for care? Who will treat?

46. Lessons from Scottish HCV Plan • Epidemiologic data KEY factor, data linkage techniques developed • Clinician and Public Health leadership • Advocacy and support groups • Strong governance • Programme managed • Political partnership

47. Challenge for Ireland 2014

48. Thank you