The Changing World of Hepatitis C

Transcription

1 The Changing World of Hepatitis C Alnoor Ramji Gastroenterology & Hepatology Clinical Associate Professor Division of Gastroenterology University Of British Columbia St. Paul s Hospital Site

2 Disclosures Company Name Abbvie BI BMS Gilead Sci. Inc Hoffman LaRoche Janssen (J. & J.) Novartis Merck & Co. Vertex Pharmaceuticals Relationship Investigator, consultant Investigator, Consultant Investigator, Consultant, Speaker Investigator, Consultant, Speaker Investigator, Consultant, Speaker Nursing Support Investigator, Consultant, Speaker Investigator Investigator, Consultant, Speaker Nursing Support Investigator, Consultant, Speaker

3 Objectives Epidemiology and natural history Burden of disease in Canada Screening Treatment options & Outcomes Fibrosis evaluation

4 Estimated 170 Million Persons With HCV Infection Worldwide 3-4 million newly infected each yr worldwide Prevalence of infection > 10% 2.5%-10% 1%-2.50% NA World Health Organization Available at: Accessed October 28, 2009.

5 HCV Infection: Worldwide Genotype Distribution 1a, 1b 2a, 2b, 3a 1a, 1b 2a, 2b, 2c, 3a 4 4 1b, 3a 2a 1b, 6 1b 1a, 1b, 2b, 3a 5a 3b 1b, 3a Fang et al. Clin Liver Dis

6 HCV Prevalence Age and gender distribution of anti-hcv positive cases in Canada (2011). 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% Males (2011) Females (2011) Myers R. et al.. Can J Gastroenterol Hepatol May;28(5):

7 Prevalence (000) Total number of viremic HCV cases (with uncertainty intervals) by year ( ) Myers R. et al.. Can J Gastroenterol Hepatol May;28(5):

8 Proportion of all viremic HCV cases according to disease stage ( ). 100% 90% Liver Transplant HCC Decomp Cirrhosis Cirrhosis F3 F2 F1 Chronic HCV (F0) 80% 70% 60% 50% 40% 30% 20% 10% 0% Myers R. et al.. Can J Gastroenterol Hepatol May;28(5):

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11 Importance of Screening and Treating HCV HCV-related mortality exceeds mortality from HCV 1 HIV: human immunodeficiency virus 1. Ly et al. Ann Intern Med. 2012;156:

12 HCV Prevalence According to Exposure *Other modes of transmission include sexual, occupational, nosocomial and vertical transmission. IDU: injection drug use. 1. Remis RS. Final Report. Public Health Agency of Canada Available from: 12

13 CDC Recommendations (August 2012) Screening of those born between ,2 *** In Canada : CLF suggests One-time testing during a yearly checkup or as a part of insurance blood work In the US, >75% of adults with chronic hepatitis C are baby boomers 73.4% of HCV-related deaths were in persons years of age CDC: Centers for Disease Control and Prevention 1. Hepatitis C: Proposed Expansion of Testing Recommendations, Available from: 2. Centers for Disease Control and Prevention. Available from: 13

14 Liver Related Mortality % What about patients with advanced disease? Long-term follow-up of patients with F3/F4 post-treatment LR-Mortality, % year 10-year occurence occurrence SVR: SVR: 1.9% %(95%CI CI ) ) Non-SVR: non-svr: 27.4% ((5% (95%CI ) Non-SVR p<0.001 SVR Van de Meer et al JAMA Follow-up time, years SVR eliminates liver failure & liver-related death

15 SVR (%) The Advancing Present DAAs 100 PegIFN Standard IFN 1991 RBV IFN 6 mos 16 IFN 12 mos IFN/RBV 6 mos IFN/RBV 12 mos PegIFN 12 mos PegIFN/ RBV 12 mos Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring, MD. PegIFN/ RBV/ DAA PegIFN/ RBV/ DAA Or DAA+RBV

16 HCV Lifecycle and DAA Targets Receptor binding and endocytosis Fusion and uncoating Transport and release (+) RNA LD ER lumen LD Virion assembly Translation NS3/4 and polyprotein protease processing inhibitors ER lumen Membranous web LD NS5B polymerase RNA replication inhibitors NS5A* inhibitors *Role in HCV lifecycle not well defined Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:

17 The Present: SVR Rates With Boceprevir or Telaprevir in Genotype 1 Treatment-Naive Patients Triple Therapy for upto 48 Weeks SVR (%) PegIFN/RBV Poordad F, et al. N Engl J Med. 2011;364: Jacobson IM, et al. N Engl J Med. 2011;364: F0-2 F3-4 BOC or TVR + PegIFN/RBV

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19 2014 /2015 :Virologic Response to PEG-INF + RBV + Simeprevir or Sofosbuvir in Genotype 1 Treatment-Naive Patients SVR (%) Jacobson I, et al. EASL Abstract Reproduced with permission. Lawitz E, et al. EASL Abstract Reproduced with permission % 90% 80% % No Cirrhosis Cirrhosis Simeprevir No Cirrhosis Sofosbuvir Cirrhosis

20 2014 /2015 :Virologic Response to PEG-INF + RBV vs. Sofosbuvir + RBV (all-oral) in Genotype 2 and 3 Treatment-Naive Patients SVR (%) % 92-94% % PegIFN/RBV X 24 wks Poordad F, et al. N Engl J Med. 2011;364: Jacobson IM, et al. N Engl J Med. 2011;364: Geno 2 SOF+RBV X 12 wks Geno 3 SOF+RBV X 24 wks Gane E, et al. J Hepatol. 2013;58(suppl 1):S3. Abstract 5. Lawitz E, et al. N Engl J Med. 2013;368:

21 2015 /2016 :Virologic Response to Non-interferon based therapy: Genotype 1 :Treatment-Naive Patients: Non-cirrhotic and cirrhotic sub-groups SVR (%) % % SOF/ LDV +/- RBV x12 wks ABT 450/rtv + ombitasvir + dasabuvir+/-rbv X 12 wks Feld JJ, et al. N Engl J Med. 2014;370: Afdhal N, et al. N Engl J Med 2014; 2014 Apr 12 Poordad F, et al. EASL Abstract O163

22 Fibrosis is the key

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25 Hepatitis C: Summary HCV is common Screening for HCV is imperative baby-boomers and immigrants Viral eradication / cure in 70-90% Viral eradication has a mortality benefit