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What’s New in Hepatitis C

What’s New in Hepatitis C. Diana L. Sylvestre , MD University of CA, San Francisco OASIS Clinic, Oakland, CA. Disclosure Information What’s New In Hepatitis C Diana Sylvestre , MD. I have the following financial relationships to disclose: Speaker’s Bureau for Merck

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What’s New in Hepatitis C

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  1. What’s New in Hepatitis C Diana L. Sylvestre, MD University of CA, San Francisco OASIS Clinic, Oakland, CA

  2. Disclosure InformationWhat’s New In Hepatitis CDiana Sylvestre, MD I have the following financial relationships to disclose: Speaker’s Bureau for Merck I will discuss the following off label use and/or investigational use in my presentation: Treating drug users for hepatitis C

  3. What’s Not New

  4. NIH Consensus Statement on HCV, 2002 “HCV therapy has been successful even when thepatients have not abstained from continued drug or alcohol use... Thus, it is recommended that treatment of active injection drug use be considered on a case-by-case basis, and that active injection drug use in and of itself not be used to exclude such patients from antiviral therapy.”

  5. NIH Consensus Statement on HCV, 2002 “HCV therapy has been successful even when thepatients have not abstained from continued drug or alcohol use... Thus, it is recommended that treatment of active injection drug use be considered on a case-by-case basis, and that active injection drug use in and of itself not be used to exclude such patients from antiviral therapy.”

  6. HCV Virology • + ssRNA:Flavivirus • 1012virions/day • Frequent mutations and no proofreading • Results in HCV variants called quasispecies Lee W et al. Drugs. 2004;64(7):693-700.

  7. HCV Prevalence by Selected GroupsUnited States Hemophilia Injection drug users HIV patients Hemodialysis STD clients Gen population adults Surgeons, PSWs* Pregnant women Military personnel Average Percent Anti-HCV Positive * PSWs (personal-service workers) are individuals whose occupations involve close personal contact with clients (e.g., hairdressers, barbers, estheticians, cosmetologists, manicurists, pedicurists, massage therapists). Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.

  8. What’s Not New

  9. Heroin-associated Mortality Hser, Y. I., et al. (2001) Arch Gen Psychiatry, 58, 503-8.

  10. n = 1042, with 4 or more serum ALT level measurements during 25 months of follow-up Patients withPrior IllicitDrug Use PersistentlynormalALT IntermittentlyelevatedALT PersistentlyelevatedALT HCV Testing: ALT Inglesby TV et al.Hepatology. 1999;29:590-596.

  11. HCV Screening Test: Has the patient been exposed? • Antibody-based EIA • Not diagnostic of active infection • Remains positive after spontaneous clearance or treatment-related cure

  12. Viral Tests: Does the patient actually have HCV? Qualitative PCR Quantitative PCR Is HCV present? How much HCV is present? Genotype What type of HCV is present?

  13. What IS New

  14. Remote (>15 yrs ago) Recent (<15 yrs ago) Injection Drug Use Injection Drug Use Transfusion Transfusion Unknown Other* Unknown Sexual Other* Sexual * Nosocomial, occupational, perinatal Relative Importance of Risk Factors for Hepatitis C Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset

  15. What’s new in testing

  16. IL-28B

  17. Noninvasive tests for liver fibrosis

  18. APRI • {(AST/upper normal AST)/platelet count} x 100 • Predicts fibrosis >1.5; and cirrhosis >2.0 • Low chance of fibrosis if < 0.5 • FIB-4 • (age x AST)/ (platelet count x ALT) • Predicts fibrosis >1.0 and cirrhosis > 3.25 Note: all platelet counts in 1000’s ( ie 100K = 100)

  19. Fibrosure

  20. Fibroscan

  21. New medications

  22. Boceprevir • NS3/4A protease inhibitor • Indicated for genotype 1 HCV in combination with peg-interferon and ribavirin • 800 mg (4 pills) tid with light meal • Treatment algorithm:4 week peg IFN + ribavirin lead in • Triple therapy for 24-44 weeks • Duration of treatment 28 – 48 weeks based on response and previous treatment • CYP 3A4: lots of interactions

  23. RESPOND-2: SVR Rates With Boceprevir vs. Prior Response • SVR rates with boceprevir-based triple therapy higher among previous relapsers vs previous partial responders to pegIFN/RBV therapy (previous null responders excluded from study) • Both groups had higher SVR rates vs pegIFN/RBV alone 100 Previous partial response 75 80 Previous relapse 69 60 52 SVR (%) 40 40 29 20 7 n/N = 23/57 72/105 30/58 77/103 2/29 15/51 0 BOC RGT BOC/PR48 PR48 Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.

  24. Telaprevir • NS3/4A protease inhibitor • Indicated for genotype 1 HCV in combination with peg-interferon and ribavirin • 750 mg (2 pills) tid with 20g fat • Treatment algorithm: • Triple therapy for 12 weeks • Complete 24-48 week treatment with pegIFN + riba • CYP 3A4: lots of interactions

  25. REALIZE: SVR Rates With Telaprevir vs. Prior Response • SVR rates with telaprevir-based triple therapy higher among previous relapsers vs previous partial responders vs null responders to pegIFN/RBV • All groups had higher SVR rates vs pegIFN/RBV alone T12/PR48 LI T12/PR48 Pbo/PR48 Previous Relapsers Previous Partial Responders Previous Null Responders 100 88* 83* 80 59* 60 54* SVR (%) 40 33* 29* 24 15 20 5 2/37 121/145 124/141 16/68 29/49 26/48 4/27 21/72 25/75 n/N= 0 Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. *P < .001 vs Pbo/PR48

  26. Drug-drug interactions • Methadone • CYP 3A4, 2B6, 2D6 • Buprenorphine • CYP 3A4, 2C8 • TVR levels vs. methadone/buprenorphine • BVR levels vs. methadone/buprenorphine • Methadone vs TVR/BVR • Buprenorphine vs. TVR/BVR • Van Heeswijk, R, Vandevoorde, A, et al. The pharmacokinetic interaction between methadone and the investigational HCV protease inhibitor telaprevir. 46th Annual Meeting of the European Association for the Study of the Liver 2011, Abstract 654. • Victrelis Package Insert, 2012.

  27. The Pipeline

  28. Phase 3, early 2013

  29. ATOMIC trial

  30. ATOMIC trial

  31. Abbott

  32. Abbott

  33. Treatment as prevention • Magiorkinis G, Sypsa V, et al. Integrating phylodynamics and epidemiology to estimate transmission diversity in viral epidemics. PLoS One, 2013;9(1):e1002876. • Durier, N, Nguyen, C, and White, LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One, 2012;7(4):e34548.

  34. Increasing treatment coverage • Durier, N, Nguyen, C, and White, LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One, 2012;7(4):e34548.

  35. Increasing treatment coverage • Durier, N, Nguyen, C, and White, LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One, 2012;7(4):e34548.

  36. Treating earlier • Durier, N, Nguyen, C, and White, LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One, 2012;7(4):e34548.

  37. Treating earlier • Durier, N, Nguyen, C, and White, LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One, 2012;7(4):e34548.

  38. Summary • New tests • IL-28B • Noninvasive fibrosis tests • New medications • Improved outcomes – genotype 1 • More challenging • Impressive pipeline • Interferon-free regimens • Better tolerability • Shorter duration • Improved response • Elimination of HCV?

  39. From: Scott J____ <sc____@gmail.com>Subject: Former PatientTo: oasisclinic@sbcglobal.netDate: Thursday, June 18, 2009, 10:48 AM

  40. Dear Dr. Sylvestre and Staff ,I am unsure if you remember me or not. In 2005 I took the hep C treatment at your clinic, but had to quit the chemotherapy earlier than planned, as Ihad an opportunity to move to Arkansas. I have had several tests done, the last being a few weeks ago, and the results are still good; no hep C detected !I have been off of drugs for almost 4 years now, have a wife and a 17 month old son in Arkansas. I am working a good job, and starting college in the fall to get a degree to teach high school English. It feels like a good way to give back to the community.

  41. I wanted to write and say thank you, from the bottom of my heart. I was in a very bad place, and had made some incredibly bad choices and would probably be dead without your help . It blows my mind how lucky I was to receive treatment for both my addiction and my Hep C, for free. Incredible that both are in remission at this point, I couldn't have done it without you.So thank you again, I cannot express the warmth I feel for you in my soul. You helped me save myself, and at a time when I thought there was no hope for me.Sincerely , S____ J_____PS I have sent a picture of me and my son, Amis, hiking in the Ozark mountains.

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