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Using genetic markers in clinical practice

Using genetic markers in clinical practice. IL28b test for chronic genotype 1 hepatitis CIL28b test for chronic genotype 2/3 hepatitis CIL28b for acute hepatitis CFuture use of IL28b testing with DAA. Recovery. Persistence. Ge, Nature, 2009; Thomas, Nature 2009; Rauch Gastroenterology 2010. Seven SNPs within a 17-kb region around IL28B gene are associated with HCV recovery.

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Using genetic markers in clinical practice

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    1. Using genetic markers in clinical practice David Thomas Advisor: Merck Clinical trial: Gilead and Merck

    2. Using genetic markers in clinical practice

    4. Seven SNPs within a 17-kb region around IL28B gene are associated with HCV recovery

    5. Seven SNPs within a 17-kb region around IL28B gene are associated with HCV recovery

    6. Estimated to be responsible for 11.7% of the variation in SVR (cf 3-4% - ethnicity / VL / fibrosis)Estimated to be responsible for 11.7% of the variation in SVR (cf 3-4% - ethnicity / VL / fibrosis)

    9. Independent replication of the effect of genetic variation in SNPs near IL28B and SVR

    12. Using genetic markers in clinical practice

    14. Favorable IL28b genotype may be associated with relapse of genotype 3 HCV infection

    16. Using genetic markers in clinical practice

    17. C allele associates with higher probability of spontaneous clearance of HCV

    18. Persons with acute hepatitis C and unfavorable IL28b genotype should be treated sooner

    19. Using genetic markers in clinical practice

    20. EOT and SVR according to rs12979860 genotype 72 patients Telaprevir/PegIFN/RBV for total duration of 12 or 24 weeks 44 (61%) of 72 had svr45 vs 67 in longer arm44 (61%) of 72 had svr45 vs 67 in longer arm

    21. SPRINT-2 Treatment-Nave Patients Stopping Rule: Patients with detectable HCV-RNA at week 24 were discontinued from treatment for futility. Peginterferon (P) administered subcutaneously at 1.5 g/kg once weekly, plus Ribavirin (R) using weight based dosing of 600-1400 mg/day in a divided daily dose. BOC administered 800 mg TID. Stopping Rule: Patients with detectable HCV-RNA at week 24 were discontinued from treatment for futility. Peginterferon (P) administered subcutaneously at 1.5 g/kg once weekly, plus Ribavirin (R) using weight based dosing of 600-1400 mg/day in a divided daily dose. BOC administered 800 mg TID.

    22. RESPOND-2 Previous Treatment Failure Stopping Rule: Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. Peginterferon (P) administered subcutaneously at 1.5 g/kg once weekly, plus Ribavirin (R) using weight based dosing of 600-1400 mg/day in a divided daily dose. BOC administered 800 mg TID. Stopping Rule: Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. Peginterferon (P) administered subcutaneously at 1.5 g/kg once weekly, plus Ribavirin (R) using weight based dosing of 600-1400 mg/day in a divided daily dose. BOC administered 800 mg TID.

    23. Distribution of IL-28B Polymorphisms

    26. IL-28B CC polymorphism is a strong predictor of TW8 response*

    27. Early Interferon Response (Lead-In) Further Defines Likelihood of Success For Non-CC Patients

    30. Checked data. The ones genotypes were enriched for greater differences78 vs 75% svr with T12 and 38 vs 46 SVR with PR. Even among CC patients, RVR occurred in 84% of CC in t12 vs 16% in PR(that is too low). Note 69% svr in ideal (thompson et al) Checked data. The ones genotypes were enriched for greater differences78 vs 75% svr with T12 and 38 vs 46 SVR with PR. Even among CC patients, RVR occurred in 84% of CC in t12 vs 16% in PR(that is too low). Note 69% svr in ideal (thompson et al)

    31. REALIZE (retreatment) Study Design Data from T12/PR48 and LI T12/PR48 arms were pooled since no differences were observed between TVR arms. Randomization was stratified by viral load and prior response. Stopping rules were applied for TVR (Weeks 4, 6, 8 for T12/PR48, Weeks 8, 10, 12 for LI T12/PR48) and PR (Weeks 12, 24, 36 for T12/PR48, Weeks 16, 24, 36 for LI T12/PR48) Data from T12/PR48 and LI T12/PR48 arms were pooled since no differences were observed between TVR arms. Randomization was stratified by viral load and prior response. Stopping rules were applied for TVR (Weeks 4, 6, 8 for T12/PR48, Weeks 8, 10, 12 for LI T12/PR48) and PR (Weeks 12, 24, 36 for T12/PR48, Weeks 16, 24, 36 for LI T12/PR48)

    32. SVR Rates by IL28B Genotype and Prior Response

    33. Viral Breakthrough Rates by IL28B Genotype and Prior Response

    34. Relapse Rates by IL28B Genotype and Prior Response

    35. IL28b C allele use is even less clear beyond boceprevir and telaprevir

    36. More potent HCV regimens will overwhelm IL28b C allele advantage

    37. Clinical Applications of IL28b Testing in HCV genotype 1 infection

    38. Clinical Applications of IL28b Testing in HCV genotype 1 infection

    40. SNPs on chromosome 20 strongly associated with Hb decline at week 4

    41. Predicted ITPA deficiency is associated with less Hb decline at treatment week 4

    42. Population Frequency of ITPA deficiency

    43. Protective mechanism of ITPA deficiency is not known but does not impact SVR

    45. Clinical application of ITPA testing

    46. Personalized Medicine for Hepatitis C

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