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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

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
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

nih consensus statement on hcv 2002
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.”

nih consensus statement on hcv 20021
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.”

hcv virology
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.

slide8

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.

heroin associated mortality
Heroin-associated Mortality

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

hcv testing alt

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.

hcv screening test has the patient been exposed
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
slide14

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?

relative importance of risk factors for hepatitis c

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

slide20

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)

boceprevir
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
respond 2 svr rates with boceprevir vs prior response
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.

telaprevir
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
realize svr rates with telaprevir vs prior response
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

drug drug interactions
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.
treatment as prevention
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.
increasing treatment coverage
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.
increasing treatment coverage1
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.
treating earlier
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.
treating earlier1
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.
summary
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?
slide46

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.

slide47

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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