Hepatitis C What’s New

1. Hepatitis CWhat’s New Alan Kilby, M.D. Portland Gastroenterology Center Maine Medical Center VTC Sept 27, 2013

2. Disclosures Maine Medical Ctr VTC Funding Schering, Merck, Vertex Experimental Drugs Discussed Sofosbuvir, Simeprevir, Ledipasvir This talk is not FDA approved

3. Hepatitis CWhat’s New 1. Test baby boomers (1945-65) 2. Exciting new treatments 2014? Sofosbuvir, Simeprevir 2015? One pill a day possible 3. Fibroscan-liver fibrosis test 4. ECHO-Telemedicine Project

4. Test Baby Boomers Birth Cohort 1945-1965: Prevalence of hep C=3.5% Infected in 1960’s thru 1980’s 75% of hep C cases, 2-3 million Only 45% report a risk factor At least 45% unaware; often think they are tested with routine labs Even with risk factors, test rate low Antiviral treatment rates are very low

5. Test Baby Boomers 75% Hep C Deaths: Baby Boomers Liver Failure and Liver Cancer Median Age of Death is 57 years After 20 years of infection: 20% Cirrhosis, 5% Liver mortality Cirrhosis, Liver cancers, deaths increase with each decade

6. Test Baby Boomers CDC has Patient Information Sheet Recommended testing: 1. HCV antibody 2. Positive HCV antibody triggers HCV RNA testing. 3. I strongly encourage reflex HCV RNA testing on same sample

7. Test Baby Boomers HCV RNA positive patients Alcohol counseling Hepatitis A and B vaccination I recommend CBC, CMP, INR, Ultrasound of Abdomen, HCV Genotype, HBsAg, HIV Ab Evaluation for HCV treatment

8. Test Baby Boomers Benefits of Rx with SVR(Cure) 1. Liver decompensation greatly reduced 2. Liver Cancer risk reduced 3. Study of 16,000 US Veterans demonstrated 55% reduction in all cause mortality

9. Hepatitis CWhat’s New 2. Exciting new treatments 2014? Sofosbuvir, Simeprevir 2015? One pill a day possible

10. Genotype and Viral Load in US Patients Genotype 4,5,6 High Viral Load Genotype 4,5,6 Low Viral Load 2.7% 1.3% Genotype 2,3 Low Viral Load 7.3% 14.7% Genotype 2,3 HVL Genotype 1 HVL 49.5% Genotype 1 LVL 24.5% Alter et al. N Engl J Med. 1999;341;556-562. Blatt et al. J Viral Hepatitis. 2000;7:196-202.

11. Sustained Viral Response:Before 2011 • Peg-Interferon Weekly + Ribavirin Daily Genotype 1 SVR=40% 48 week treatment Wt-based ribavirin Genotypes 2,3 SVR=80% 24 week treatment Low dose ribavirin (800 mg)

12. Flu-like symptoms Headache Fatigue or asthenia Myalgia, arthralgia Fever, chills Neuropsychiatric disorders Depression Mood lability Alopecia Thyroiditis Nausea Diarrhea Injection-site reaction Lab alterations Neutropenia Anemia Thrombocytopenia Side Effects of Interferon

13. Side Effects of Ribavirin • Hemolytic anemia • Teratogenicity • Cough and dyspnea • Rash and pruritus • Insomnia • Anorexia COPEGUS™ (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.

14. Hepatitis CTreatment Since 2011 Direct-Acting Antivirals Protease Inhibitors Boceprevir (Victrelis) Telaprevir (Incivek) Triple Therapy- PEG-Interferon/Ribavirin/Protease Inhibitor for genotype 1, 24-48 weeks SVR for Genotype 1: 65-75%

15. Hepatitis CTreatment Since 2011 Problems with Telaprevir/Boceprevir 1. New side effects-Rash (Telaprevir), diarrhea, nausea; increased anemia 2. Poor tolerance in cirrhotics 3. Drug Interactions (Cytochrome system): Hormonal contraceptives, HIV, transplant drugs

16. Hepatitis CTreatment Since 2011 Problems with Telaprevir/Boceprevir triple therapy Limited to genotype 1 3x per day dosing, 6-12 pills Low barrier to drug resistance Poor efficacy: Cirrhotics, prior non-responders, genotype 1a, IL28B genotype CT and TT

17. Hepatitis CTreatment: The Future HCV Life Cycle Video

18. Hepatitis CTreatment: The Future Sofosbuvir-Nucleotide HCV polymerase (NS5B) inhibitor Once a day dosing All genotypes treated Minimal side effects/drug interactions Drug resistance not observed

19. Hepatitis CTreatment: 2014 Likely FDA Approvals Sofosbuvir + Ribavirin: 1st Interferon-free treatment available Geno 2, 12 weeks, SVR 97% Geno 3, 12 weeks, SVR 56% G3 does better with 16 weeks Cirrhosis-better with 16 weeks

20. Hepatitis CTreatment: 2014 Likely FDA Approvals 12 wks Sofosbuvir/Riba/PEG-IFN Geno 1, 4, 5, 6 SVR 90% Cirrhosis 80%

21. Hepatitis CTreatment: 2014 Likely FDA Approvals Simeprevir-once-a-day protease inhibitor Simeprevir given for 1st 12 weeks PEG-IFN/Ribavirin started with simeprevir and given for 24 or 48 wks Genotype 1 SVR 83-85%

22. Hepatitis CTreatment: 2015 Drugs from 2+ classes, as in HIV Increases efficacy and minimizes resistance One Example (Many under study) NS5b and NS5a inhibitor Sofosbuvir + Ledipasvir; one pill a day; ?available 2015

23. Hepatitis CWhat’s New Fibroscan- A non-invasive liver fibrosis test FDA approved

24. FibroScan-Non-invasive test of liver fibrosis The probe induces an elastic wave through the liver The velocity of the ultrasonic shear wave is a measure of elasticity (fibrosis) Explored volume 2.5 cm 1 cm  4 cm

25. FibroScan-Non-invasive test of liver fibrosis Good accuracy in detecting cirrhosis Combined with clinical, lab, imaging results: Will likely replace liver biopsy in detection of cirrhosis Cirrhotics require additional monitoring

26. Cirrhosis: Preventive Measures No Alcohol Vaccines: Pneumonia, Flu, Hepatitis A and B Screen for Esophageal Varices Screen for Liver Cancer

27. Hepatitis CWhat’s New ECHO-Telemedicine Project

28. ECHO-Telemedicine Project Central site: Education/support Remote sites: Treat patients Come online together: Didactic session + Case Presentations Goal: Increase treatment at the local level, especially in remote areas Coming to Maine!

29. Dr. Kilby wants One pill a day treatment for PCP. Treats all patients regardless of genotype, severity of liver disease, presence of co-morbidities. Requires minimal monitoring and has few side effects, drug interactions or drug resistance. Non-invasive testing for cirrhosis