1. Hepatitis C When, how and which patients should be treated Graham R Foster Professor of Hepatology Queen Marys School of Medicine Barts and The London

2. JC 34 year old man Infected with genotype 1 HCV (ALT 120) Refuses liver biopsy

3. JC 34 year old man Infected with genotype 1 HCV Refuses liver biopsy Single Lives in a rented flat does not drink

4. JC 34 year old man Infected with genotype 1 HCV Refuses liver biopsy Single Lives in a rented flat does not drink Methadone prescription – 80 mls/day

5. JC 34 year old man Infected with genotype 1 HCV Refuses liver biopsy Single Lives in a rented flat does not drink Methadone prescription – 80 mls/day Injects heroin x3 per week/ crack ‘ occasionally’

6. JC Should we treat him ?

7. HCV in 2006 Not treating Jason Good reasons/Bad reasons

8. HCV in 2006 Not treating Jason Good reasons/ Bad reasons He does not have bad disease

9. HCV in East London Prevalence of cirrhosis in Pakistani/Bangladeshi patients presumably infected at birth D’Souza et al Clin Gastro Hep 2005

10. HCV in East London Prevalence of cirrhosis in Pakistani/Bangladeshi patients presumably infected at birth D’Souza et al Clin Gastro Hep 2005

11. HCV in East London Prevalence of cirrhosis in Pakistani/Bangladeshi patients presumably infected at birth D’Souza et al Clin Gastro Hep 2005

12. HCV in East London

13. Therapy for HCV: Who should receive therapy? Risk of liver damage Need for biopsy Therapy Young people Low If they wish!

14. Therapy for HCV: Who should receive therapy? Risk of liver damage Need for biopsy Therapy Young people Low If they wish! Middle aged ModerateHighIf they wish or have fibrosis

15. Therapy for HCV: Who should receive therapy? Risk of liver damage Need for biopsy Therapy Young people Low If they wish! Middle aged ModerateHighIf they wish or have fibrosis ElderlyHigh Only if they have bad disease

16. HCV in 2006 () I am seeing increasing numbers of patients from Bangladesh and Pakistan with advanced liver disease from HCV

17. HCV in 2006 () Are we missing something ? The government tells us that this is a drug users disease I am seeing non-drug users with liver cancer secondary to HCV Are we missing something important ?

18. HCV in 2006 Not treating Jason Good reasons/ Bad reasons He does not have bad disease – but he will get it!

19. HCV in 2006 Not treating Jason Good reasons/ Bad reasons He does not have bad disease – but he will get it! He is unlikely to respond

20. Sustained Response Rates in HCV Genotype 1 – 40 KD PEG IFNα2a + Ribavirin 24 weeks48 weeks SVR (%) 29% 41% 40% 51% n=101n=118n=250n=271 PEG IFN RBV 800 PEG IFN RBV 1000/1200 PEG IFN RBV 800 PEG IFN RBV 1000/1200 Hadziyannis et al Ann Intern Med 2004:140;346-355

21. Effects of age and SVR ( Data from patients treated with 40 KD PEG IFNα2a and Ribavirin) 20 60 Age (completed life-years) 555045352520 30 40 50 60 70 80 90 Calculated SVR Rate (%) 4030 Foster et al AASLD 2003

22. Sustained Response Rates in HCV Genotype non 1 – 40 KD PEG IFNα2a + Ribavirin SVR (%) 24 weeks48 weeks 78% 73% 77% n=106n=162n=111n=165 PEG IFN RBV 800 PEG IFN RBV 1000/1200 PEG IFN RBV 800 PEG IFN RBV 1000/1200 Hadziyannis et al Ann Intern Med 2004:140;346-355

23. Treating the non-1 patient Can we use shorter durations of therapy ? Pilot study of 14 weeks therapy in patients with an early virological response Used Peg-Intron 1.5  g/kg + Normal dose ribavirin Dalgard et al Hepatology 2004:40:1260-1265

24. Treating the non-1 patient Can we use shorter durations of therapy ? SVR (by per protocol analysis) of patients with an early virological response receiving 14 weeks therapy

25. Peg-IFN and Ribavirin Today The standard algorithms are being revised Easy to treat patients may need shorter durations of therapy

26. Peg-IFN and Ribavirin Today The standard algorithms are being revised Easy to treat patients may need shorter durations of therapy Easy to treat patients are young with no fibrosis!

27. HCV therapy tomorrow BILN 2061 New protease and polymerase inhibitors are on the way

28. HCV in 2006 Not treating Jason Good reasons/ Bad reasons

29. Therapy in difficult patient groups

30. HCV – Who should we treat? (Opinion based medicine) We should NOT treat active drug users They will not comply They will get reinfected (They are not worth it)

31. HCV in drug users - evidence Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up. Dalgard O, Bjoro K, Hellum K, Myrvang B, Skaug K, Gutigard B, Bell H; The Construct Group. Eur Addict Res 2002 Jan;8(1):45-9 Treatment of hepatitis C infection in injection drug users Markus Backmund, Kirsten Meyer, Michael Von Zielonka, Dieter Eichenlaub Hepatology July 2001 Volume 34 p188 to p193

32. HCV in drug users Drug users infect others ! Not treating drug users encourages the spread of HCV

33. Treating the untreatable 27 patients started therapy (13 Genotype 1) Completed = 10Early cessation = 2Completed 3 months = 11 4 PCR +ve7 PCR -veETR = 9 (SVR 3/3) i.e. by Intent to treat analysis 16/23 = 70% have an EVR

34. Treating the untreatable 27 patients started therapy (13 Genotype 1) Completed = 10Early cessation = 2Completed 3 months = 11 4 PCR +ve7 PCR -veETR = 9 (SVR 3/3) ALL patients have benefited from the attention – two are looking for work!

35. Therapy for HCV Summary (I) The natural history of HCV is of glacial progression Many patients will eventually develop cirrhosis Delaying therapy may reduce response rates

36. Therapy for HCV Summary (II) We have effective therapies available and these can be given to ALL patients with chronic HCV

37. Therapy for HCV Who would treat Jason ?

38. Therapy for HCV Post Script JC was offered therapy He agreed to undergo therapy and has completed 9 months treatment He has not injected for 3 months He has been offered a job in his brothers shop