1. Hepatitis C Update September 2015 Amy C. Smith, FNP

2. Hepatitis C Identified 1989 Testing available 1992 Non-A, Non-B Blood-borne infection No vaccine available Leading cause of liver transplant

3. Hepatitis C According to CDC – New infections: 21,870/ year – Chronic infections: 2.7 – 3.9 M Does not include prisoners, homeless, institutionalized – Annual deaths: 15,000 In 2007, HCV deaths > HIV deaths Prevalence – US:3-5 M – Worldwide:170 M

4. Epidemiology VERY high rate with IV illicit drug use – 60% all new infections – Single largest risk category High rate in correctional institutions – 31% + (2000) Incarceration + IV drug use EXTREMELY high – Up to 91% in one state facility tested – General assumption is ~ 80%

5. Epidemiology Other risks: – Blood products and transplants before 1992 – Multiple sexual partners (? 4+) – Intranasal drug use – “Unclean” body piercing or tattoos – Occupational exposure – Dialysis – Tattooing/piercings – Low socioeconomic level – ETOH – ??? Many unknown source

6. Epidemiology VERY low risk: – Mother to fetus – Non-sexual household contact Razors, toothbrushes, clippers – Sexual transmission in monogamous relationship

7. Epidemiology NOT SPREAD BY: – Sneezing – Coughing – Food/water – Sharing utensils or drink – Handshake or holding hands – Hugging – Kissing – Playing – Donating blood

8. Overview HCV – Acute Self-limited Rare hepatic failure Typically leads to chronic infection – 20% clear spontaneously: + HVC Ab, - HCV RNA (PCR) – Chronic Progressive course over many years Can result in cirrhosis and HCC Can result in need for transplant

9. Overview

10. Fibrosis seems to be more rapid with: – Duration of infection – Older age at exposure – Male – Co-infection with Hep B or HIV – Heavy ETOH use – Ongoing drug use – Obesity – Cigarette and marijuana smoking Fibrosis --> Cirrhosis – Compensated: extensive scarring but liver still works fairly well – Decompensated: very extensive scarring and liver function is compromised Portal HTN, Ascites, Varices, Encephalopathy, Coagulopathy

11. Overview Cirrhosis: – 3% to 5% will develop Hepatocellular Carcinoma (HCC) – Incidence of HCV decreasing, but number of cirrhotics and ESLD increasing – Expected to peak 2020 - 2030 – Many will need transplant Cost of transplant: $577,100 Cost of annual anti-rejection meds: $30,000

12. Symptoms Many have NO symptoms Non-specific, mild, intermittent – Fatigue – Headache – Insomnia – Dark Urine – Joint pain – Pruritus – Jaundice

13. Evaluation Who to test: – USPSTF: everyone born 1945 – 1965 – Received blood products or organ before 1992 – IV drug use (even ONCE) – Chronic liver disease – HIV – Abnormal LFTs – Exposure to known HCV + blood – Hemodialysis – Mother with HCV

14. Diagnosis Check HCV Ab – If positive, confirm with HCV RNA (PCR) Genotype: – 7 different genotypes – In US, 70% are genotype 1 29% genotype 2 or 3 Subtypes Immigrants Liver biopsy – Gold standard for assessing fibrosis – >Stage 3, easier to get treatment – Risks – Options of noninvasive “biopsy” Fibroscan, Fibrosure, Fibrospect, Hepascore Limitations

15. Diagnosis CBC CMP TSH Hep A and B panel – Acute panel does not tell immunity status – HAV IgM Ab, HBV sAg, HBV core IgM, HCV Ab – Must add HAV IgG, HBV sAb, HBV core Ab total HIV AFP PT/INR Iron, ferritin US

16. Diagnosis Once confirmed, then check HCV RNA Quantitative and Genotype – Gives specific genotype and viral load to direct treatment

17. Management AASLD and IDSA joint guidelines (2014) www.hcvguidelines.org Treatment: – Direct Antiviral therapy (cornerstone) – Psychological counseling – Symptom management – Dose adjustment of medications – Assessment of fibrosis – Screening for cirrhosis/complications

18. Management If no antibodies for Hep A and B, should get vaccinated Screening for depression at diagnosis and subsequent visits Support group Fatigue – Cause uncertain – ? From liver disease vs depression/other – Improves with SVR – ?? Zofran

19. Management Counseling – Routes of HCV transmission – Risk of infecting household contacts – Lifestyle factors that promote hepatic fibrosis

20. Management Dose Adjustment of Medications – Try to avoid NSAIDs in advanced liver disease – Do not need to avoid acetaminophen, but do not exceed 2g/24 hours – Available data FAILS to show an increased risk of adverse effects with compensated chronic liver disease and statins Safe in stable HCV Associated reduction in portal pressure with cirrhotics

21. Management Screening – Cirrhotic: Esophageal varices – EGD Hepatocellular Carcinoma – U/S, AFP tumor marker

22. Goal of Antiviral Therpay Eradicate HCV RNA (SVR) SVR = cure of the HCV infection Decrease: – All-cause mortality – Liver-related death – Need for liver transplant – HCC rates – Liver-related complications Including those with advanced liver fibrosis – Reduce transmission ULTIMATE GOAL: achieve undetectalbe HCV RNA level – SVR at 12 or 24 weeks post-treatment completeion – Longterm clearance 99% – SVR: virologic cure

23. Antiviral Therapy Direct acting antivirals has changed the face of treatment and who we should treat – Vast majority of patients are candidates – Special consideration: Chronic kidney disease Liver transplant HCC Highly effective (98-100% SVR) All-oral regimens – Interferon-free – Also Ribavirin-free in some cases

24. Antiviral Therapy $$$$ Media attention in the US $95,000 (8 weeks) to $145,000 (12 weeks) Even at high introductory cost, they are cost- effective Superior efficacy: 98-100% Does limit access for some

25. Antiviral Therapy Treatment selection based on GENOTYPE – Genotype 1 – Genotype 2 and 3 – Genotype 4, 5, 6, 7

26. Antiviral Therapy Two main new drugs for Genotype 1 – Harvoni (Sofosbuvir/Ledipasvir) – Viekira Pak (Ombitasvir/paritaprevir/ritonavir + dasabuvir) In combination with Ribavirin

27. Harvoni Adverse Events – > 10%: headache, fatigue – > 5%: nausea, diarrhea, insomnia Drug Interactions – Contraindication: Rifampin, St. John’s Wort – PPI, H2-blockers, antacids: can alter absorption (dose separately)

28. Harvoni Treatment-naïve, no cirrhosis, viral load < 6M: 8 weeks (97% clearance) Treatment-naïve, with or without cirhosis, viral load > 6 M: 12 weeks (99% clearance) Treatment-experienced, without cirrhosis: 12 weeks (99% clearance) Treatment-experienced, with cirrhosis: 24 weeks (100% clearance)

29. Harvoni Price – 8 weeks: $63,000 – 12 weeks:$94,500 Highlights: – One pill once daily – With or without food – No Indication for ESRD – ? Genotype 4

30. Viekira Pak Competition for Harvoni As effective as Harvoni A little cheaper: 12 weeks for $88,000 3 pills in AM, 1 pill in PM PLUS weight-based Ribavirin (usually 2 pills twice daily) Must be taken with food Ribavirin has increased drug interactions and must monitor labs closely (every 2-4 weeks) – CBC, CMP, TSH, INR

31. Viekira Pak Genotype 1a: – Without cirrhosis: 12 weeks – With cirrhosis: 24 weeks Genotype 1b: – Without cirrhosis: (NO RIBA) 12 weeks – With cirrhosis: 24 weeks

32. Who Should Be Treated? My theory: almost everyone – Exceptions: ESRD, ongoing drug and/or ETOH abuse Insurance company’s theory: almost noone – Want stage F3-F4 fibrosis (cirrhosis) before approval – Exclusion clauses – Numerous appeals and denials AASLD highest priority: – Advanced fibrosis, compensated cirrhosis, pre- and post-transplant, Severe extra-hepatic complications

33. Who Should Be Treated? If 2 appeal failures with insurance, Gilead (Harvoni) will pay for treatment Similar program for Viekira GREAT options for uninsured through the pharm companies

35. Resources AASLD Guidelines Hcvguidelines.org UptoDate CDC