1. Clinical managment of hepatitis C in an environment with limited acces to treatment Andrzej Horban Hospital of Infectious Diseases Warsaw, Poland

2. What means ” limited access” ? 1.Epidemiological situation 2.Surveillance study 3.Health care financing 4.Inclusions and exclusions criteria 5.Schema of treatment 6.Monitoring principles

3. Therapeutic programmes in limited resources countries Who should be treated ? –Staging –Grading

4. HCV Epidemiology in Poland 2004 - 2157 2005 - 2342 2006 - 2890 2007 - 2693 Since 1990, when the anti-HCV tests were introduced 18 years x 2000 -2500 persons = 36 000 – 45 000 persons = appr. 0,1 % of population ?

5. HCV Epidemiology in Poland Cities: 6.5 / 100 000( male -7.1, female 6,0) Countryside: 2.9 / 100 000 ( male -3.6, female 2.1) Male: 20-24 years – 10,8 /100 000 Female: 60-64 years - 9,4/ 100 000 Czaszkowski M., Kuszewski K., Przegl Epid 2005; 59(2):303-8 National Hygiene Institute Report 2006

6. HCV in Poland: therapeutic programs Therapeutic programs supported by National Health Fund 2000 procedures carried out in 63 centres Number of treated is limited to 2500 per year (patients are on waiting list)

7. Therapies in Poland Number of centres in Poland – 63 Number of therapies per month in all the centres – 1569 From 1 therapy (Łuków) to 250 (Warsaw Hospital of Infectious Diseases)

8. Therapeutic programme using pegylated interferon in the treatment of CHC – reimbursed by the National Health Fund (NFZ) in Poland Pegylated interferon alpha in the treatment of chronic hepatitis C 1. Pelylated interferon alpha 2a 2. Pegylated interferon alpha 2b 3. other interferons

9. Inclusion criteria for CHC treatment programmes – in Poland presence of HCV RNA in the serum or hepatic tissue determination of the number of HCV RNA units in the tested material determination of viral genotype chronic hepatitis and compensated cirrhosis

10. Inclusion criteria for CHC treatment programmes – in Poland inflammatory lesions and fibrosis in the histopathology of the liver (patients with genotype 2 or 3 and those with contraindications for biopsy do not require liver biopsy) patients with extrahepatic manifestations of HCV infection should be treated irrespective of disease severity in the histopathological score age - now no limitation

11. Exclusion criteria for CHC treatment programmes only medical contraindication

12. HCV in Poland: therapeutic programmes – pegylated interferon alpha Pegylated interferon alpha may be used in patients above 18 years of age in monotherapy – in patients with contraindications to ribavirin in combination with ribavirin – in patients with chronic hepatitis C, with recurrent infection or after an unsuccesfull treatment with interferon alpha or interferon alpha with ribavirin

13. Therapeutic programmes – pegylated interferon alpha Treatment of chronic hepatitis C is dependent on the genotype, early viral response and extrahepatic manifestations of HCV infection: patients with genotype 2 or 3: 24-weeks therapy note: in patients with genotype 3, in which undetectable HCV RNA was not achieved after 24 weeks and with liver fibrosis (staging) > 2: therapy up to 48 weeks

14. Therapeutic programmes – pegylated interferon alpha patients with genotype 1 or 4: therapy depending on the early viral response and staging - patients with liver fibrosis (staging) </= 2, decreasing viraemia greater than 2 log is not seen after 12 weeks of treatment – therapy should be discontinued but -in patients with liver fibrosis > 2 therapy should be continue up to 48 weeks irrespective of reduction in viraemia

15. Therapeutic programmes – pegylated interferon alpha patients with extrahepatic manifestations of HCV infection should be treated for 48 weeks irrespective of genotype and reduction in viraemia after 12 weeks

16. Therapeutic programmes – pegylated interferon alpha 2008 : in patients infected with HCV of genotype 1 (Pegasys or Pegintron) or genotype 4 (Pegasys), with viraemia < 600 000 IU/ml at beginning of treatment and undetectable HCV RNA after 4 weeks (RVR) it is recommended to cut the duration of therapy down to 24 weeks

17. Therapeutic programmes in Poland – outcome monitoring Since last year, a based internet system was introduced to monitor proper programme conducting It covers patient’s data at the point of admittance to the programme (personal ID, weight, drug name, dose, biopsy results, genotype, viraemia level),RVR, EVR, ETR, SVR, reasons for interruption of treatment

18. Bosnia&Herzegovina Population - 3 500 000 HCV Prevalence - % (number) -1 ( 35 000) Number of diagnosed – 554 Number of treated - 543 % treated of diagnosed - 98 treatment reimbursment - no Limitation - yearly budget for treatment given every year by government

19. Bosnia&Herzegovina Inclusion criteria - full diagnostic: HCV RNA (+), biopsy, genotype Exclusion criteria – age( over65), drug addiction (drug addicts, or less than 1 year of abstinence) Hospitals/Ambulatories – beginnging in hospitals, continue in outpatients clinics Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks Monitoring– 12,48,72 weeks Response Guided Therapy - only with permission

20. Estonia Population – 1 300 000 HCV Prevalence - % (number) - 1,5 ( 19 500) Number of diagnosed - NA Number of treated - NA % treated of diagnosed - NA Full treatment reimbursment - yes Limitation - no

21. Estonia Inclusion criteria - full diagnostic: HCV RNA (+), biopsy, genotype Exclusion criteria – Hospitals/Ambulatories – Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks Monitoring– 4,12,48,72 weeks Response Guided Therapy - Yes

22. Hungary Population – 10 000 000 HCV Prevalence - % /number– 0.70/ 70 000 Number of diagnosed - 1000 Number of treated - 1000 % treated of diagnosed – 100 Full treatment reimbursment - yes Limitation - no

23. Hungary Inclusion criteria - full diagnosis: HCV RNA (+), biopsy, genotype Exclusion criteria – only medical contrindication Hospitals/Ambulatories – hepatology outpatients clinics Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks Monitoring – 12,48,72 weeks Response Guided Therapy - Yes

24. Czech Republic Population – 10 200 000 HCV Prevalence % /number– 0.20/ 20 400 Number of diagnosed - 2000 Number of treated - 600 % treated of diagnosed – 30 Full treatment reimbursment - yes Limitation - no

25. Czech Republic Inclusion criteria - full diagnostic: HCV RNA (+), biopsy, genotype Exclusion criteria – active drug addicts Hospitals/Ambulatories – ambulatories Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks/ sometimes 48 weeks Monitoring – 12,48,72 weeks Response Guided Therapy – not yet

26. Bulgaria Population – 7 700 000 HCV Prevalence % /number – 1.38/ 106 260 Number of diagnosed - 2072 Number of treated - 300 % treated of diagnosed – 14.48 Full treatment reimbursment - yes Limitation - yes, only 300 yearly

27. Bulgaria Inclusion criteria - full diagnosis: HCV RNA (+), biopsy, genotype, elevated Alat Exclusion criteria – NA Hospitals/Ambulatories – ambulatories Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks/ sometimes 48 weeks Monitoring – 12,48,72 weeks Response Guided Therapy – not yet

28. Slovenia Population – 2 000 000 HCV Prevalence - % /number– 1.38/ 106 260 Number of diagnosed – approximately 2000 since 1993, 115 in 2008 Number of treated - 115 % treated of diagnosed – Full treatment reimbursment - yes Limitation - no

29. Slovenia Inclusion criteria - full diagnosis: HCV RNA (+), biopsy, genotype, elevated AlAT Exclusion criteria – NA Hospitals/Ambulatories – ambulatories Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks Monitoring – 12,48,72 weeks Response Guided Therapy – not yet

30. Romania Population – 19 600 00 HCV Prevalence - % /number– 4.90/ 960 400 Number of diagnosed – approximately 2100 Number of treated - 420 % treated of diagnosed – 20% Full treatment reimbursment – 100% Pegasys, 25% Copegus Limitation - no

31. Romania Inclusion criteria - full diagnosis: HCV RNA (+), age = 1, genotype, normal or elevated AlAT, naive or relapser ( Not NR) Exclusion criteria – age >65, liver biopsy <1 Hospitals/Ambulatories – ambulatories Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks Monitoring – 12,48,72 weeks Response Guided Therapy – not yet

32. Macedonia Population – 2 000 000 HCV Prevalence - % /number – 1,20/ 24 000 Number of diagnosed - 1326 Number of treated - 360 % treated of diagnosed – 27,15 Full treatment reimbursment – yes for limited group of patients Limitation - yes - hospital budget

33. Macedonia Inclusion criteria - elevated ALT, biopsy result - hepatic damage Exclusion criteria – drug users with less than 6 months abstinence Hospitals/Ambulatories – hospitals Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks/ Monitoring – 12,48,72 weeks Response Guided Therapy – not yet

34. Russia Population – 142 200 000 HCV Prevalence - % /number– 1,30/ 1 848 600 Number of diagnosed – 77 000 Number of treated - 20 000 % treated of diagnosed – 25,97 Full treatment reimbursment – no Limitation - only some group of patience (cirrhosis, diabetes, haemophilia).Regional AIDS centres receive Pegays for treatment HIV-HCV coinfected pts in the frame of National priority project „Health”

35. Russia Inclusion criteria Exclusion criteria Hospitals/Ambulatories – ambulatories Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks/ Monitoring – 4,12,48,72 weeks Response Guided Therapy – yes

36. Croatia Population – 4 400 000 HCV Prevalence - % /number– 1,4/ 61 600 Number of diagnosed – 700 Number of treated - 320 % treated of diagnosed – 45,71 Full treatment reimbursment – yes Limitation - hospitals

37. Croatia Inclusion criteria - HCV – RNA positive, age 2x), Normal ALT activity (F2 and more) normal or high, liver biopsy score >= F1 Exclusion criteria – Hospitals/Ambulatories – hospitals Treatment rules Genotype 1,4 – 48 weeks Treatment rules Genotype 2,3 – 24 weeks/ Monitoring– standard 12,48,72 week, week 4 only in pts with genotype 1 with low wiremia Response Guided Therapy – yes

38. Therapeutic programmes in limited resources countries Lack of surveillance study Gap between estimated seroprevalence and reality Access to treatment is limited

39. Therapeutic programmes in limited resources countries Who should be treated ? –Staging ? –Grading ?