Carlo Cammà Cattedra di Gastroenterologia Università di Palermo carlomma@unipa.it

1. Il management del paziente difficile nelle infezioni virali croniche Definire e trattare il paziente “difficile” HCV monoinfetto Carlo Cammà Cattedra di Gastroenterologia Università di Palermo carlo.camma@unipa.it Roma 25 Novembre 2010

2. HCV DifficulttoTreatPatients Metabolic Factors HCV-infected Patient Virological Factors Severity of fibrosis Genetic factors

3. HCV DifficulttoTreatPatients Metabolic Factors HCV-infected Patient Virological Factors Severity of Fibrosis Genetic factors

4. HCV DifficulttoTreatPatients Effetto medio Mega-trial The promise of personalized medicine

5. Genetics Predict Response: IL28B Genotype C/C Confers Higher SVR Rates D. Ge, Nature , 2009

6. Rate of SVR and rs12979860 C-allele frequency in diverse ethnic groups. DL Ge et al.Nature461, 399-401 (2009) doi:10.1038/nature08309

7. Genetics Predict Response: IL28B Genotype C/C Confers Higher SVR Rates SVR (%) 29 114 79 10 51 47 4 22 8 n = T/T T/C C/C T/T T/C C/C T/T T/C C/C T/T* T/C* Gt 1 Gt 2/3 Gt 4 C/C* *Genotype of rs12979860 on chromosome 19 (Ge D et al. Nature. 2009;461:399-401).Strättermayer A et al. EASL 2010.

8. HCV DifficulttoTreatPatients E’ la risposta all’interferone interamente correlata al polimorfismo genetico ? NO

9. IL28b and outcome of combinationantiviraltherapy with PEG-IFN + Riba Balagopal et al. Gastroenterology 2010

10. HCV DifficulttoTreatPatients Metabolic Factors HCV-infected Patient Virological Factors Severity of fibrosis Genetic factors

11. 233 Cirrhotic pts (ITT analysis) HCV DifficulttoTreatPatients Patients with virological response (%) Di Marco V et al, personal data

12. HCV DifficulttoTreatPatients E’ la risposta all’interferone interamente correlata al polimorfismo genetico e alla fibrosi ? NO

13. IDEAL study HCV DifficulttoTreatPatients Gastroenterology 2010;139:120-9

14. HCV DifficulttoTreatPatients Metabolic Factors HCV-infected Patient Virological Factors Severity of fibrosis Genetic factors

15. HCV DifficulttoTreatPatients • (HEPATOLOGY 2006) Steatosis (± visceral obesity) and IR hyporesponsiveness to antiviral therapy.

16. HCV DifficulttoTreatPatients IR and SVR in G1 Chronic Hepatitis C ROMERO-GOMEZ et al, Gastroenterology 2005

17. HCV DifficulttoTreatPatients LowVit D SVR Hepatology, 2010

18. HCV DifficulttoTreatPatients Menopause and SVR Factors Associated with SVR MV analysis in 442 Female Patients with CHC Villa et al., submitted

19. HCV DifficulttoTreatPatients Metabolic Factors RapidVirologicalResponse asStrongestPredictorof SVR HCV-infected Patient Virological Factors Severity of fibrosis Genetic factors

20. HCV DifficulttoTreatPatients RVR Range RVR in G1 10% - 50%

21. HCV DifficulttoTreatPatients RVR 24 wks PR

22. BaselinePredictorsof RVR in NaivePatientswith G1 CHC Low Baseline HCV-RNA IL28B Gene RVR Vitamin D Levels Absenceof Severe Fibrosis Lower BMI LDL-COL Insulin Resistance Steatosis

23. IL-28B and RVR

24. IL 28 RVR LowVit D

25. HCV Difficult to Treat Patients IDEAL study

26. Differences between Peg 2-a and 2-b • Pharmacodinamic profile Peg 2-a Peg 2-b RVR 4 wk Triple therapy

27. DAA

28. DAA TELAPREVIR (T)

29. DAA BOCEPREVIR (BOC)

30. DAA LEAD-IN

31. HCV DifficulttoTreatPatients 3 scenari clinici • IL-28B • LEAD IN RVR • TRIPLICE

32. PR 24 wks LEAD-IN RVR

33. Naive IL28 TT 40% NR TRIPLICE

34. ???? Naive IL28 TC LEAD-IN: ??? TRIPLICE

35. HCV DifficulttoTreatPatients TRASFERIBILITA’ RISULTATI MEGA-TRIAL

36. Non tutto ciò che può essere misurato conta, e non tutto ciò che conta può essere misurato. Albert Einstein

37. Disclaimer Servizio scientifico offerto alla Classe Medica da MSD Italia S.r.l.Questa pubblicazione riflette i punti di vista e le esperienze dell’autore [o degli autori] e non necessariamente quelli della MSD Italia S.r.l. Ogni farmaco menzionato deve essere usato in accordo con il relativo riassunto delle caratteristiche del prodotto fornito dalla ditta produttrice. 01-13-RTG-2010-IT-4769-AV