1. From discovery to cure in 25 years -- the Hepatitis C story Mel Krajden MD, FRCPC Medical Head, Hepatitis Acting Medical Director, Public Health Laboratory BC Centre for Disease Control Professor, Pathology & Laboratory Medicine, UBC

2. Liver Cancer

3. Non-A, Non-B Hepatitis - 1980’s 80% to 90% of post- transfusion hepatitis Blood products used to treat hemophiliacs Dialysis People who inject drugs Needlestick injuries 10% to 25% - sporadic Limited sexual & transmission from mother to child

4. Agent was a Virus 30 to 60 nm in size because filtration prevented transmission 100,000 viruses fit across the width of hair Lipid coated – treatment with solvents prevented transmission He et al. J Inf Dis 1987 Bradley et al. Gastroenterol 1985 All efforts to identify the agent had failed!

5. DNA RNA blood Lambda GT-11 E. Coli factories1 in a million! cDNA

6. Cutting edge genomics to identify, clone and express Non-A, Non-B virus proteins - hepatitis C virus (Hep C) (Choo et al. and Kuo et al. Science 1989) First antibody test – used for blood screening & diagnosis c-100 Enzyme Patient’s Antibody Wall Street Journal - May 11, 1988

7. 5'UTR CNS3 4A 4BNS5ANS5B 3 'UTR E1E2NS2 Capsid protein Envelope glycoproteins Ion channel Cystein protease p7 Serine protease RNA helicase RNA dependent RNA polymerase Phosphoprotein NS3 protease cofactor ?

8. Blood products are now screened & safe People who inject drugs account for about 80% of current infections in the developed world Unsafe injection practices is a big problem in the developing world Limited sexual & about 5% of infected mothers transmit to their child Understand Hep C Transmission

9. Mohd Hanafiah et al. Hepatology 2013;57:1333–1342 Estimated ≈ 185 M People Worldwide Infected

10. 1.5% of British Columbians are infected about 70,000 people Four major groups: People who inject drugs, about 30% to 70% 25% to 60% are also HIV co-infected Baby boomers (1945-1965), about 3% Immigrants, about 3% Aboriginal People about 3% to 7.5% Hep C

11. No vaccine for Hep C – one for Hep A & B Only 25% of people display symptoms 25% will clear infection 75% will stay infected Of those with chronic infection, one in four will develop cirrhosis, end stage liver disease, liver cancer, or require liver transplantation Disease progression takes decades Worse with alcohol and obesity Natural History of Hep C

12. ~50% curable - Interferon-based drugs >95% Curable - Direct Acting Antivirals

13. Curing Hep C: (Hill et a.l 2014) 62-84% reduction in deaths 68-79% reduction in liver cancer 90% reduction in the need for liver transplantation

14. How best to test/screen those affected? Who/when to treat? Cost! Prioritize treatment to those that need it most - avert existing health system costs? Provider capacity? Questions Facing Policy Makers

15. Genomic Methods to Understand Transmission

16. Understanding Transmissions

17. BC Hepatitis Testers Cohort All medical visits All hospitalizations All prescribed drugs Some risk data Cancer treatments All death data De-identified health information for 1.5 million British Columbians tested for Hep C, HIV and hepatitis B Includes almost all: lab tests/results, medical visits, hospitalizations, prescriptions, cancer outcomes, and mortality 25-years of information Costs of services Health outcomes by different groups Amongst the most comprehensive in the world Lab tests

18. Science & Genomics to Prevent Hep C and Cure Infections – Elimination! 3515 55 25 65 45 Age Screening and treating older people -Prevent serious liver disease / liver cancer / need for transplant Preventing infection among younger people -Harm reduction -Interrupt transmission networks -Treatment as prevention? $ $ TransmissionsDisease

19. Scientific Discovery Better Health Programs Policies Scientific Discovery Better Health Programs Policies