The Dawn of a New Era: Hepatitis C

Transcription

1 The Dawn of a New Era: Hepatitis C Naudia L. Jonassaint Assistant Professor of Medicine and Surgery University Pittsburgh School of Medicine December 1, 2015

2 Objectives After presentation the learner should understand: Basic epidemiology of Hepatitis C Appropriate screening for Hepatitis C Treatment of the disease Identification of special populations

3 Hepatitis C: significant health burden Leading cause of transplantation in the US 1-5% of infected population will eventually die of complications of cirrhosis or liver cancer The burden of disease increases with age and disease severity The total cost expected to rise from 6.5 billion in 2012 to 9.1 billion in Razavi et al. Hepatology Jun. 57(6):

4 Progression to cirrhosis happens over decades

5 Progression to cirrhosis happens over decades treatment 4-6 million persons in the US

6 Population Studies Show a Significant Gap in Hepatitis C Care in the United 3.5 Million 79% Genotype (GT) % States US Cascade of Care, % 16% 9% Chronic HCV infection Diagnosed and aware 1. Yehia BR, et al. PLoS One. 2014;9:e Zein NN, et al. Ann Intern Med. 1996;125: Access to outpatient care Prescribed HCV treatment Achieved sustained virologic response (SVR)

7 Patients Should be Screened for HCV According to Birth Cohort and Risk Factors 1,2 PATIENT SCREENING FOR HCV Birth Cohort Screening Persons Born Between 1945 and ,2 The birth cohort was selected on the basis of HCV prevalence and disease burden One-time screening for HCV infection in the birth cohort may identify infected patients at earlier stages of disease 1. Smith BD, et al. MMWR Recomm Rep. 2012;61: Moyer VA; US Preventive Services Task Force. Ann Intern Med. 2013;159: Risk Factor Based Screening Important Risk Factors 1,2 Past or current injection drug use Receiving a blood transfusion before 1992 Long-term hemodialysis Being born to an HCV-infected mother Incarceration Intranasal drug use Getting an unregulated tattoo Other percutaneous exposures

8 There are 6 Hepatitis C genotypes

9 Reality of Treatment Degree of Fibrosis Matters

10 What is seen under the microscope?

11 What is seen under the microscope?

12 Many noninvasive ways of measuring fibrosis Castera. Gastrenterology 2012:142;

13 Most common noninvasive measurement being used currently in US is Fibroscan (TE)

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15 Fibroscan converted to Metavir and used for treatment decision making

16 Treatment

17 HCV Can Now Be Cured in Most Patients Unlike HIV and HBV infection, HCV infection is a curable disease What does cure mean? Sustained Viral Response Undetectable HCV RNA 12 weeks after completion of antiviral therapy for chronic HCV infection Long term morbidity and mortality benefits Ghany MG, et al. Hepatology. 2009;49(4):

18 There has been Rapid Improvement in Treatment Options 100% 90% Sustained Virological Response 80% 60% 40% 20% 6% 16% 34% 42% 39% 55% 75% IFN IFN IFN/R IFN/R PegIFN PegIFN/R PR/PI PR/SOF 6 mo 12 mo 6 mo 12 mo 12 mo 12 mo 6-12 mo 3 mo

19 Multitargeted Approach for Treatment: Protease Inhibitors, Polymerase Inhibitors and NS5A Inhibitors Simeprevir Asunaprevir Paritaprevir **MORE COMING SOON Ledipasvir Daclatasvir Ombitasvir Sofosbuvir McGovern B, Abu Dayyeh B, and Chung RT. Hepatology. 2008; 48: Dasabuvir

20 Genotype 1

21 Sofosbuvir/Ledipasvir Combination for Hepatitis C Genotype 1 Ledipasvir Once-daily, oral, 90 mg NS5A inhibitor LDV NS5A inhibitor Sofosbuvir Once-daily, oral, 400-mg NS5B inhibitor SOF nucleotide polymerase inhibitor Ledipasvir/Sofosbuvir FDC Once-daily, oral fixed-dose (90/400 mg) combination tablet Single-tablet regimen for hepatitis C FDC, fixed-dose combination. LDV NS5A LDV inhibitor NS5A inhibitor SOF SOF SOF SOF nucleotide nucleotide polymerase polymerase nucleotide inhibitor inhibitor polymerase inhibitor 21

22 GT 1 Treatment-Naïve Non-cirrhotic: Treatment Duration LDV/SOF 8 Weeks (N=215) LDV/SOF 12 Weeks (N=216) SVR12 94% (202/215) 96% (208/216) Relapse Rates Overall <6 M IU/mL >6 M IU/mL 5% (11/215) 2% (2/123) 10% (9/92) 1% (3/216) 2% (2/131) 1% (1/85) 8 week LDV/SOF regimen should only be considered in GT 1, treatment-naïve, non-cirrhotic patients with BL viral load <6 million IU/mL Ledipasvir/sofosbuvir (HARVONI ) Prescribing Information. Gilead Sciences, Foster City, CA. October, 2014 (Adapted from Table 6).

23 LDV/SOF + RBV for 12 vs 24 Weeks: SVR12 in GT 1 Treatment-experienced Cirrhotic Patients (ION- 2) PI+PEG/RBV Failure PEG/RBV Failure SVR12 (%) 12/14 7/8 11/13 7/9 14/14 8/8 13/13 9/9 LDV/SOF LDV/SOF + RBV LDV/SOF LDV/SOF + RBV 12 Weeks 24 Weeks Afdhal et al. N Engl J Med 2014;370:

24 GT 1 Treatment-naïve and Treatment-experienced Paritaprevir/r (protease inhibitor/ritonavir) + ombitasvir (NS5A inhibitor) + dasabuvir (non-nucleoside polymerase inhibitor) + RBV (3D + RBV) Also known as Viekira Pak

25 Viekira Pak works well in treating Hepatitis C genotype 1 L. Molloy, PharmD, Childrens Hospital of Michigan, Detroit, Michigan

26 ALLY-2 trial: efficacy of daclastasvir+ sofosbuvir in HIV co-infected patients

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29 Currently Available Regimens Recommended in the AASLD/IDSA Treatment Guidance Document GT 2 and GT 3 Patients

30 Sofosbuvir (nucleotide polymerase inhibitor) + Ribavirin GT 2 and GT 3 Treatment-naïve and Treatment-experienced

31 AASLD/IDSA Guidance for Genotype 2 GT 2 Treatment Naïve SOF + RBV for 12 weeks Treatment Experienced SOF + RBV for 12 weeks (patients with cirrhosis may should be extended to 16 weeks)

32 SOF+RBV: IFN Free Regimen Available for GT 2 and GT 3 Infected Patients Genotype 2 Genotype 3 SOF + RBV 12 weeks N=73 SOF + RBV 24 weeks N=250 Overall SVR 93% (68/73) 84% (210/250) Outcome for subjects without SVR On-treatment virologic failure 0% (0/73) <1% (1/250) Relapse 7% (5/73) 14% (34/249) Treatment-naïve 3% (1/32) 5% (5/105) Treatment-experienced 10% (4/41) 20% (29/144) Other 0% (0/73) 2% (5/250)

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34 AASLD/IDSA Guidance for Genotype 3 GT 3 Treatment Naïve or Experienced DAC+ SOF for 12 weeks (non-cirrhotic) DAC + SOF ± RBV for 24 weeks (cirrhotic) SOF + RBV + PEG-IFN for 12 weeks

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36 Future approaches Different therapeutic targets Shorter therapy Pangenotypic approaches Multiple drugs Expanded populations (renal failure) Primary care treatment

37 Conclusions The cure of Hepatitis C will change the face of medicine, hepatology and transplant surgery Screening is to be most important step in the future of Hepatitis C The wave of the future will be pangenotypic treatment with one pill daily or less Those patients with Hepatitis C and advanced liver disease and other special populations need to be referred to hepatology

38 Thank You