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Hepatitis C Nut and Bolts (2008) - Nevah-Rubin, Ilan

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  • 1. Hepatitis C
  • 2. Characteristics RNA virus + sense 9.6 Kb in length Flaviviridae -> hepaciviridae -> HCV
  • 3.  
  • 4. HCV, HBV, HIV: Prevalence vs Undiagnosed Cases * Extrapolated from small population study. 1. American Liver Foundation. Hepatitis C Factsheet . Available at: www.liverfoundation.org. Accessed May 11, 2007. 2. NIAID. HIV Infection and AIDS: An Overview . 2005. Available at: www.niaid.nih.gov. Accessed May 14, 2007. 3. Lok A, et al. Hepatology . 2004;39:1-5. 4. Thompson MJ, et al. J Cancer Educ . 2002;17:222-226. * 3.5 M 2.5 M 1.5 M .5 M 0
  • 5. Statistics
    • 170 Million infected worldwide
    • 2.7-3 Million active infection nationwide
    • High medical costs - $600 Million
    • 30K New infections/year
    • 10K Deaths/year
    • Most important causes of Liver Disease
    • OLT
  • 6. HCV Genotypes
    • Hepatitis C virus
      • RNA virus–high mutation rates
      • Evolved different genotypes
    • 6 known genotypes
      • Genotype 1 (75%)
      • Genotype 2 (10%)
      • Genotype 3 (10%)
    • The above 3 are the most common in the United States
    • Little difference in mode of transmission or natural history of infection among different genotypes
    Flamm SL. JAMA. 2003;289:2413-2417 . Distribution of HCV Genotypes 75% 10% 10% 5% Genotype 1 Genotype 2 Genotype 3 Other
  • 7. Prevalence of HCV in Select Populations Alcoholics ~240,000 (11%–36%)5 HIV-infected ~300,000 (30%) 4 Living below poverty level ~940,000 (2.4%) 6 Incarcerated ~330,000 to 860,000 (16%–41%)1 Veterans ~280,000 (8%) 8 IDU ~300,000 (80%–90%)2,3 Homeless ~175,000 (22%) 7 Children (6 – 18 years old) ~100,000 (.1%) 9
    • Adapted from the following:
    • CDC. MMWR. 2003;52(RR-1):1-33. 2. Edlin B. Hepatol. 2002;36(5 suppl 1):S210-219. 3. NHSDA Report 2003. 4. Poles M, et al. Clin Infect Dis . 2000;31:154-161. 5. LaBrecque D, et al: Hepatitis C Choices . 2002:7-15. 6. Alter M, et al. N Engl J Med . 1999;341:556-562. 7. Nyamathi A, et al. J Gen Intern Med . 2002;17:134-143. 8. Bräu N, et al. Am J Gastroenterol . 2002;97:2071-2078. 9. Jonas M. Hepatol . 2002;36(5 suppl 1):S173-S178. 10. Armstrong GL, et al. Ann Intern Med. 2006;144:705-714.
  • 8. Prevalence of HCV in Racial/Ethnic Populations
    • Adapted from the following:
    • Armstrong GL, et al. Ann Intern Med . 2006;144:705-714.
    • US Census Bureau. Available at:: www.census.gov. Accessed March 21, 2007.
    In 2005, it was estimated that over 41 million Latinos lived in the United States. The Latino population is a diverse population. US census data show that the Latino population consists of nearly 64% Mexican Americans. 2 * * P < 0.005 for comparison with reference group (Non-Hispanic White) 1 1.5% 3% 1.3% 0 1 2 3 4 5 Prevalence of Antibodies to HCV Prevalence of Antibodies to HCV (%) Non-Hispanic White Non-Hispanic Black Mexican American
  • 9. Hepatitis C Virus Infection Prevalence by Age 0 1.0 2.0 3.0 4.0 5.0 < 11 11-19 20-29 30-39 40-49 50-59 60-69 ≥ 70 Age Group Anti-HCV Positive (%) Alter MJ, et al. N Eng J Med. 1999;341:556-562 .
  • 10.  
  • 11. HCV replication and infection Adapted from Pawlotsky JM, Gish RG. Antivir Ther 2006;11:397-408
  • 12. Hepatitis C Virus Fate of Acute Infection 15% Chronic 85% Spontaneous resolution Alter MJ, et al. N Eng J Med. 1999;341:556-562 .
  • 13. Natural History
  • 14. Hepatitis C Virus Infection Natural History Stable 80% (68%) HCC Liver failure 25% (4%) Slowly progressive 75% (13%) Resolved 15% (15%) Acute HCV Cirrhosis 20% (17%) Chronic HCV 85% (85%) ETOH HIV Fe Hepatic viruses
  • 15. Hepatitis C Virus Infection Population at Risk
      • Ever injected illegal drugs / intranasal cocaine use
      • Tattoo and Body piercing
      • Received clotting factors made before 1987
      • Received blood/organs before July 1992
      • Ever on chronic hemodialysis
      • Evidence of liver disease
      • Incarceration
      • Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood
      • Children born to HCV-positive women
    Centers for Disease www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm Control and Prevention. Hepatitis C fact sheet.
  • 16. Testing Strategies for HCV RF for HCV and/or Abn LFT’s Anti HCV (EIA) testing < 5% Chance of HCV Prior exposure to HCV HCV VL + Genotype RIBA NO HCV Exposed + Cleared Refer for evaluation and Tx. NO HCV HCV VL + Genotype positive negative
  • 17. Hepatitis C Virus Diagnostic Testing Diagnostic Test Type Confirmation Screening Use 2-6 weeks 2-6 months Detection postexposure > 98% Variable Specificity > 98% > 95% Sensitivity Virus Virologic Antibodies Mode of detection Serologic Specifications
  • 18.
    • False positives
      • Autoimmune disorders
      • Spontaneous resolution of viral infection
    • False negatives
      • Chronically immune suppressed
      • Transplant recipients
      • Chronic renal failure on dialysis
      • HIV positive
    HCV Antibody Testing Limitations
  • 19. Physical Exam
    • Non Specific (Malaise / Weakness)
    • Chronic liver disease
      • Palmar Erythema Temporal Wasting
      • Gynecomastia Spider Angiomas
      • Caput Medussa Dupuytren’s contracture
      • Clubbing Asterixis
      • Icterus Enlarged Parotid
      • Testicular atrophy HSM
  • 20. Extrahepatic Manifestations
    • Autoimmune / Rheumatological
      • Mixed Cryoglobulinemia, Sj ö gren and Arthritis
    • Hematological
      • NHL
    • Endocrinological
      • Thyroid and DM
    • Dermatological
      • PTC and Lichen Planus
  • 21. Laboratory Evaluation
    • CBC
    • BMP
    • LFT’s
    • TFT’s
    • HIV
    • Viral Hepatitis
    • Genotype
    • Viral Load
    • Liver Biopsy
    • A1C
    • Hemochromatosis (Fe Studies)
    • A1-AT
    • Wilson’s Dz
    • Autoimmune
      • ANA, RF, AMA
  • 22. Hepatitis C Virus Infection Liver Biopsy
    • Only test that can accurately assess
      • Severity of inflammation
      • Degree of fibrosis
    • Determines the following
      • Risk for developing cirrhosis in future
      • Need for therapy
      • Need for ongoing therapy when initial treatment has failed
  • 23. Liver Biopsy (Metavir)
  • 24. Who to treat? Innocent until proven guilty Treatment until proven otherwise
  • 25. Who to treat?
    • Age 18
    • Liver Enzyme elevation
    • Liver Biopsy (Stage dependant ?)
    • Compensated Liver Disease (Tbili, INR, Alb, Plt, HE, Ascites)
    • Hematologic parameters (Hb, WBC, Cr)
    • Controlled depression
  • 26. Who NOT to treat?
    • Major/Uncontrolled depressive disorder
    • Renal/Lung/Heart Transplant
    • Autoimmune Hepatitis
    • Uncontrolled hyperthyroidism
    • Pregnant – Unwilling to go contraception
    • Age under 3
    • Hypersensitivity
    • Severe Disease: HTN, CHF, CAD, DM, COPD
  • 27. Goals of Treatment
    • Sustained Virological Response
    • Prevent the progression of Cirrhosis
    • Reduce Risk of HCC
  • 28. Factors Associated With SVR
    • Pretreatment or fixed
    • Genotype
    • HCV RNA level
    • Histology
    • Race
    • HIV coinfection
    • Steatosis / IR?
    • Body weight
    • Adherence
    • Dynamic factors
    • Rapid virologic response (HCV RNA negative at Wk 4)
    • Early virologic response
      • Partial (HCV RNA decline of > 2 logs at Wk 12)
      • Complete (HCV RNA negative at Wk 12)
  • 29. SVR in Patients Who Achieved an RVR 90 282 257 9 GT 1 GT 2 GT 3 GT 4 100 86 86 88 Patients With an RVR RVR: HCV RNA negative (< 50 IU/mL) at Wk 4 Fried MW, et al. EASL 2008. Abstract 7. 0 20 40 60 80 100 SVR (%) n =
  • 30. Calculating a Cure: Pretreatment Characteristics
    • Likelihood of SVR depends on interactions of multiple factors
    • Can individual probabilities of SVR be estimated?
    • Data from 2 registration trials of pegIFN-2a + RBV used to identify important factors related to SVR
    • Modeling used to vary important baseline characteristics
    Foster GR, et al. Scand J Gastroenterol. 2007;42:247-255.
  • 31. Everyone Is Special Probability of Achieving an SVR 100 80 60 40 20 0 Patients Number 1 2 3 4 5 6 7 8 97 89 74 52 36 19 14 7 Foster GR, et al. Prediction of sustained virological response in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) and ribavirin. Scandinavian Journal of Gastroenterology. 2007;42(2):247-255. 9000 9000 9000 9000 1200 40 40 40 HCV RNA, IU/mL x 10 3 30 30 30 26 26 26 20 20 BMI 20 2 No 60 2 No 20 7 No 43 2 No 60 1 Yes 60 43 43 Age in years 1 2 2 ALT quotient No No No Cirrhosis
  • 32. Genotype 1/4 VS. Pegasys 180 mcg/week Copegus 1000 / 1200 mg/day (75kg) PEG-intron 1.5 mcg/Kg/week Rebetol 1000 / 1200 mg/day (75kg)
  • 33. Genotype 2/3 VS. Pegasys 180 mcg/week Copegus 800 mg/day PEG-intron 1.5 mcg/Kg/week Rebetol 800 mg/day
  • 34. Current Therapy of Hepatitis C
    • Based on HCV genotype
    • Genotype 1
    48 weeks PEG IFN alpha 2a 180 ug per week and RBV 1000-1200mg per day OR PEG IFN alpha 2b 1.5ug/kg per week and Ribavirin 800-1400mg/day
    • Genotype 2 or 3
    24 weeks PEG IFN alpha 2a or 2b and Ribavirin 800mg/day
  • 35. Definition: Viral Responses
    • Sustained Virological Response (SVR)
    • End of Treatment Response (ETR)
    • Non-Responders (NR)
      • Breakthrough and Null responders
    • Relapser (R)
    • Rapid Virological Response (RVR) – 4wk
    • Early Virologcal Response (EVR) – 12wk
      • cEVR
      • pEVR
  • 36. Definition: Viral Responses RVR cEVR pEVR 4 12 24 48 72 NR BT ETR SVR Rel >2log ↓ Undetectable HCV RNA <50IU/ml
  • 37. Efficacy of current HCV combination therapy by genotype 1. Hadziyannis SJ, et al. Ann Intern Med 2004;140:346-355; 2. Fried MW, et al. N Engl J Med 2002;347:975-982; 3. Manns MP, et al. Lancet 2001;358:958-965; 4. Zeuzem S, et al. J Hepatol 2004;40:993-999 1 2 or 3 42–52% response rate 1–3 Genotype 76–93% response rate 1–4
  • 38. Current Therapy of Hep C ?
  • 39. Rapid Virologic Response (RVR) Ferenci P, et al. J Hepatol . 2005;43:425 . Patients with SVR (%) HCV RNA Status Week 4 Negative ≥2 log  <2 log  ≥2 log  <2 log  Week 12 Negative Negative Negative ≥2 log  ≥2 log  Week 24 Negative Negative Negative Negative Negative PEG IFN  -2a 180 mg + RBV 1000–1200 mg 91 72 60 48 43 0 20 40 60 80 100 *Negative predictive value = 74%; positive predictive value = 75%. 91 90 90 90 65 ETR SVR
  • 40. Slow-to-Respond Patients: Extending Therapy RBV dose (mg/day) = Berg 800 Sanchez-Tapias 800 Ferenci 1000-1200 33 16 31 46 44 77 0 20 40 60 80 100 SVR (%) Berg T, et al. Gastroenterology. 2006;130:1086-1097. Sanchez-Tapias JM, et al. Gastroenterology. 2006;131:451-460. Ferenci P, et al. AASLD 2006. Abstract 390. 72 weeks 48 weeks
  • 41. SVR rate 72 wks treatment in G1 pts with pEVR
    • PegIFN alfa-2b 1.5 µg/kg/wk + RBV 800-1400 mg/day
    • HCV RNA positive at Wk 12 but HCV RNA negative at Wk 24 (N = 101 slow responders)
    • Continued treatment through 48 vs 72 wks
    • Baseline characteristics
      • 48% black
      • 78% high HCV RNA
      • 26% F3/4 fibrosis
      • 34% BMI > 30
      • 18% high fasting glucose
    Pearlman BL, et al. Hepatology. 2007;46:1688-1694.
  • 42. SVR rate 72 wks treatment in G1 pts with pEVR Pearlman BL, et al. Hepatology. 2007;46:1688-1694. Response, % 48 Wks 72 Wks P Value EOT 45 48 NS SVR 18 38 .03 Relapse 59 20 .004 Treatment cessation 14 15 NS
  • 43. ACCELERATE Trial: SVR G2/3 Pts With and Without an RVR Shiffman ML, et al. N Engl J Med. 2007;357:124-134. Patients infected with HCV genotype 2/3 (N = 1291) RVR: yes 67% (871 / 1291) SVR 378/461 370/410 55/205 105/215 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100% SVR 82% 27% 49% 90% 16 wks 24 wks 16 wks 24 wks RVR: no 33% (420 / 1291)
  • 44. Influence of Cumulative RBV: Wks 1-12 on SVR in G1 Reddy KR, et al. AASLD 2005. Abstract 596. Cumulative RBV Exposure (Wks 1-12) SVR (%) 0 20 40 100 66 57 62 45 425 < 60% 60% to 79% 80% to 96% ≥ 97% Total 80 60 n = 325 56 44 0
  • 45. Discontinuing RBV on G1 Patients Responding to Therapy *HCV RNA – negative (< 50 IU/L) patients at Week 24 randomized to continue treatment with/without RBV at Week 26. Bronowicki J, et al. Gastroenterology. 2006;131:1040-1048. PegIFN alfa-2a 180 µg/wk + RBV 800 mg/day (n = 173) PegIFN alfa-2a 180  g/wk + RBV 800 mg/day (N = 516) PegIFN alfa-2a 180 µg/wk (n = 176) Week 26 Follow-up Week 24: HCV RNA negative* Week 48 Week 72
  • 46. Discontinuing RBV oif n Patients Responding to Therapy: SVR Bronowicki J, et al. Gastroenterology. 2006;131:1040-1048. Outcome % Treatment During Last 24 Wks P Value PegIFN alfa-2a + RBV (n = 173) PegIFN alfa-2a (n = 176) SVR (ITT) 68.2 52.6 .004 SVR (PP) 71.5 56.7 .006
  • 47. Complication / Side Effect
    • PEG-Interferon alfa 2 a/b
      • Flu-like symptoms
      • Depression / Mood instability
      • Cytopenias (WBC / Plt)
      • Thyroid (hypo / hyper)
      • Alopecia
      • Nausea / Vomiting /Abdominal pain
    • Ribavirin
      • Hemolytic anemia
      • Rash
  • 48. Non-Responder / Relapser
    • New Molecules (STAT-C)
    • Clinical Trials
    • Retreatment with different PEG molecule
    • Infergen (Consensus IFN)?
    • Induction Therapy?
  • 49. Future Therapies
    • Viral Entry Inhibitors
      • HC Ig. and Monoclonal Ab.
    • HCV RNA Translation Inh.
    • Post Translational Processing Inh.
      • NS3-4A Serine Proteinase Inh.
    • HCV Replication Inhibitors
      • NS5B Polymerase Inh, Cyclophilin B Inh, NS5A Inh, Helicase Inh
    • Virus Assembly and Release Inh
  • 50. Targets for New Treatments 1) Virus Entry 2) Uncoating 3) Protein Synthesis 4) Cleavage 5) RNA Replication 6) Packaging 7) Maturation 8) Re-infection Adapted from: Pawlotsky JM, Gish RG. Future therapies for Hepatitis C. Antivir Ther. 2006;11:397-408.
  • 51.
    • Randomized, placebo-controlled, phase II trial
    PROVE 1: Telaprevir + PegIFN/RBV in Naive HCV GT1 TVR + PegIFN alfa-2a + RBV (n = 79) PegIFN alfa-2a + RBV TVR + PegIFN alfa-2a + RBV (n = 79) TVR + PegIFN alfa-2a + RBV (n = 17) PegIFN alfa-2a + RBV Treatment-naive patients infected with HCV genotype 1* (N = 250) Week 12 * Patients received TVR 1250-mg loading dose followed by 750 mg every 8 hrs or placebo based on the arm to which they were randomized. † Patients must achieve undetectable HCV RNA at Week 4 (< 10 IU/mL) and at last test before stopping therapy at 12 or 24 weeks. Week 24 Week 48 24-week † follow-up 24-week † follow-up Placebo + PegIFN alfa-2a 180  g/wk + RBV 1000/1200 mg QD (n = 75) EOT EOT SVR SVR McHutchison J, et al. EASL 2008. Abstract 4.
  • 52. PROVE 1: Response Rates (ITT) *HCV RNA < 10 IU/mL. † P = .001 vs pegIFN/RBV/placebo 48 weeks. ‡ P = .02 vs pegIFN/RBV/placebo 48 weeks. ¶ Only subjects who met the RVR criterion and stopped at 12 or 24 total weeks of treatment. § Relapse denominator is the number of subjects with undetectable HCV RNA at completion of assigned treatment duration. McHutchison J, et al. EASL 2008. Abstract 4. Treatment, % Week 4 Undetectable* Week 12 Undetectable* SVR Relapse (n/N) § PegIFN/RBV/placebo 48 wks (n= 75) 11 45 41 23 (8/35) TVR/PegIFN/RBV 12 wks  pegIFN/RBV 36 wks (n = 79) 81 80 67 † 6 (3/51) TVR/pegIFN/RBV 12 wks  pegIFN/RBV 12 wks ¶ (n = 79) 81 68 61 ‡ 2 (1/41) TVR/pegIFN/RBV 12 wks ¶ (n = 17) 59 71 35 33 (3/9)
  • 53. PROVE 1: AEs Associated With TVR
    • Gastrointestinal events, skin events (rash, pruritus), and anemia more frequent in TVR treatment arms
      • Moderate and severe rash more frequent in TVR-based treatment arms
      • Incidence and severity of other AEs similar to peginterferon alfa-2a and ribavirin alone
    • Cumulative discontinuation due to AEs by Week 12
      • TVR treatment arms: 18%
      • Peginterferon alfa-2a and ribavirin only: 4%
    • Hemoglobin levels lower in TVR arms for first 12 weeks
    McHutchison J, et al. EASL 2008. Abstract 4.
  • 54. PROVE 2: TVR + PegIFN ± RBV in HCV G1 Naive Patients Treatment- naive patients infected with HCV genotype 1* (N = 323) TVR + PegIFN alfa-2a + RBV (n = 81) TVR + PegIFN alfa-2a + RBV (n = 82) TVR + PegIFN alfa-2a (n = 78) Week 12 *Patients received TVR 1250-mg loading dose followed by 750 mg every 8 hrs or placebo based on the arm to which they were randomized. Patients received 12 or 24 weeks regardless of whether RVR occurred. Week 24 Week 48 Placebo + PegIFN alfa-2a 180 µg/wk + RBV 1000-1200 mg QD (n = 82) PegIFN alfa-2a + RBV (n = 81) Week 36 Follow-up Follow-up Follow-up Dusheiko G, et al. EASL 2008. Abstract 58.
  • 55. PROVE 2: Response Rates (ITT) Dusheiko G, et al. EASL 2008. Abstract 58. Treatment, % Week 4 Undetectable* Week 12 Undetectable* SVR ¶ Relapse (n/N) § PegIFN/RBV/placebo 48 wks (n = 82) 12 41 48 20 (9/45) TVR/pegIFN/RBV 12 wks  pegIFN/RBV 12 wks (n = 81) 69 † 73 † 68 ‡ 14 (8/56) TVR/pegIFN/RBV 12 wks (n = 82) 80 † 79 † 62 ¥ 29 (18/63) TVR/pegIFN 12 wks (n = 78) 51 62 36 48 (22/46)
  • 56. PROVE 2: Adverse Events
    • Skin events (rash, pruritus) more frequent in TVR treatment arms
      • Rash most common reason for treatment discontinuation in TVR/pegIFN/RBV treatment arms: 7% (12 of 163)
        • Macropapular rash which resolved after treatment discontinuation (median time to discontinuation: ~ 9 weeks)
    • Cumulative discontinuation due to AEs by Week 12
      • Both pegIFN/RBV/placebo 48 weeks and TVR/pegIFN 12 weeks: 10%
      • TVR/pegIFN/RBV 12 weeks: 12%
      • TVR/pegIFN/RBV 12 weeks  pegIFN/RBV 12 weeks: 16%
    • All treatment arms experienced comparable mean decreases in hemoglobin levels in the first 12 weeks
      • No incremental effect on neutrophil or platelet counts in TVR treatment arms
    Dusheiko G, et al. EASL 2008. Abstract 58.
  • 57. SPRINT-1: Boceprevir + PegIFN/RBV in Naive HCV G1 Kwo P, et al. EASL 2008. Abstract 995. PegIFN/RBV * PegIFN/RBV *+ Boceprevir † 48-week treatment arm PegIFN/RBV *+ Boceprevir † 48-week treatment arm PegIFN/low-dose RBV arm + Boceprevir † PegIFN/RBV * Follow-up Week 72 Week 48 Week 4 Week 28 Baseline Week 40: interim analysis Lead in No lead in *PegIFN alfa-2b 1.5 µg/kg/wk and weight-based RBV 800-1400 mg/day. † Boceprevir 800 mg TID.
  • 58. SPRINT-1: Undetectable HCV: Wks 4 / 12 of Boceprevir Therapy Kwo P, et al. EASL 2008. Abstract 995. 0 20 40 60 80 100 Undetectable* HCV RNA (%) 60 39 8 78 73 34 PegIFN/RBV lead-in  pegIFN/RBV + boceprevir (n = 103) PegIFN/RBV + boceprevir (n = 107) PegIFN/RBV (n = 104) *HCV RNA <15 IU/mL. Duration 4 4 -- Boceprevir Rx 12 12 -- (weeks) 8 4 4 Total Rx 16 12 12
  • 59. SPRINT-1: Highest WHO Grade Anemia 28 Weeks of Treatment
    • Epoetin-alfa treatment
      • PegIFN/RBV lead-in arm  pegIFN/RBV + boceprevir: 48%
      • PegIFN/RBV + boceprevir: 45%
      • PegIFN/RBV: 25%
    Kwo P, et al. EASL 2008. Abstract 995. Anemia Severity 0 20 40 60 80 100 Patients (%) Grade 0 23 21 45 Grade 1 Grade 2 Grade 3 Grade 4 50 54 46 27 25 10 1 0 0 0 0 0 PegIFN/RBV lead-in  pegIFN/RBV + boceprevir (n = 206) PegIFN/RBV + boceprevir (n = 226) PegIFN/RBV (n = 104)
  • 60. STEALTH C-1: NTZ + PegIFN ± RBV in G4 HCV Patients
    • Nitazoxanide (NTZ): broad-spectrum activity against parasites, anaerobic bacteria and viruses
    Rossignol JF, et al. EASL 2008. Abstract 68. 180 µg/week pegIFN alfa-2a; weight-based RBV 1000-1200 mg/day; 500 mg BID NTZ. NTZ NTZ + PegIFN NTZ + PegIFN + RBV PegIFN/RBV Follow-up Week 72 Week 48 Week 12 Baseline NTZ NTZ NTZ + PegIFN NTZ + PegIFN + RBV NTZ n = 40 n = 28 n = 28 n = 12 n = 12 IFN-naive patients IFN-experienced patients
  • 61. STEALTH C-1: NTZ + PegIFN ± RBV in G4 HCV Patients
    • 77 patients completed NTZ lead in
      • Week-12 HCV RNA reduction: 0.26 log 10 IU/mL ( P = .0032)
    • RVR (IFN-naive patients)
      • PegIFN + RBV: 38%
      • PegIFN + RBV + NTZ: 64% ( P = .048)*
    • No increase in AEs noted in NTZ arms vs SOC
    Rossignol JF, et al. EASL 2008. Abstract 68. 0 20 40 60 80 100 SVR (%) P = .023 10 30 50 70 90 50 61 79 PegIFN + RBV PegIFN + NTZ PegIFN + RBV + NTZ P = NS IFN-Experienced Patients 8 25 N = 40 28 28 12 12 IFN-Naive Patients * 16 wks total therapy (12 weeks NTZ + 4 weeks PegIFN + RBV + NTZ)
  • 62.  
  • 63.  
  • 64. Hepatitis C Future Communication and Education Research and Treatment State and Local Prevention Programs Surveillance & Screening High Risk population HCV
  • 65. HCV Prevention and Detection
    • Prevention
      • Community Education
      • Awareness
        • Risk Factors • Complications
    • Detection
      • Testing high risk populations