1. Penny R. Thayer, FNP, BC Gastro/Hepatology NP James H. Quillen, VAMC

2. OBJECTIVES  PREVALENCE  IDENTIFY RISK FACTORS  TREATMENT OPTIONS  COMMON SIDE EFFECTS OF ANTIVIRAL THERAPY  APPROPRIATE CODING

3. FACES OF THE DISEASE

4. PREVALENCE  NHANES IV (1999-2002) 1 1.6% anti-HCV positive (95% CI 1.3-1.9%) = 4.1 million persons (95% CI 3.4-4.9 million) 1.3% chronic infection = 3.2 million persons Peak prevalence age 40-49 (4.3%) Three characteristics identified 85.1% all infections: abnormal serum ALT, ever IVDU, transfusion <1992 Most persons born 1945-1964 Armstrong GL, Wasley A, Simard E, et al. Ann Intern Med 2006; 144: 705-14.

5. TESTING FOR HCV AB  Recent/past injection drug users—even if only used once  Groups with high HCV prevalence  HIV-infected individuals  Hemophiliacs treated with clotting factor concentrates before 1987  Hemodialysis recipients  Patients with unexplained aminotransferase abnormalities  Recipients of transfusion or transplantation before July 1992  Children born to women infected with HCV  Healthcare, public safety, and emergency medical personnel following needle injury or mucosal exposure to HCV-infected blood  Current sexual partners of individuals infected with HCV  Persons who have used illicit drugs by noninjection routes

6. DIAGNOSIS  Positive Hepatitis C antibody-exposure  Positive Hepatitis C RNA (PCR)  RIBA  Generally asymptomatic  Acute Hepatitis C

7. PROGRESSION  ACUTE HEPATITIS C 15-40% will spontaneously resolve, generally within the first 6-18 months after acute onset. 60-85% will progress to chronic infection  CHRONIC 85-90% stable 10-15% progress to cirrhosis

8. PROGRESSION  CIRRHOSIS 75% slowly progressive 25% progress to HCC 2-4% liver failure  HCC Risk increases for every year for a patient with chronic hepatitis C. Patients without signs of cirrhosis can develop HCC

9. PREDICTIONS BY 2019  193,000 HCV deaths 720,700 million years of advanced liver disease 1.83 million years of life lost  $11 billion in direct medical care costs  $21.3 and $54 billion societal costs from premature disability and mortality

10. RISK FACTORS  IVDU-Even ONCE  ETOH ABUSE-includes binge drinking  Multiple sex partners  Tattoos  Snorting cocaine-Even ONCE  Blood transfusions before 1991  Dialysis

11. INITIAL WORKUP  CBC  CMP  TSH  HCV PCR (VIRAL LOAD)  HCV GENOTYPE  Hepatitis A and Hepatitis B vaccine panel  HIV  AFP  Liver Ultrasound

12. MELD SCORE  http://www.mayoclinic.org/meld/mayomo del6.html http://www.mayoclinic.org/meld/mayomo del6.html  survival probability of a patient with end- stage liver disease is estimated based on the following variables.  INR, Bilirubin, Creatinine, on dialysis twice per week  Score greater 11

13. GENOTYPES  Genotype 1 Treatment naïve Relapse, partial response, null responder  Genotype 2 & 3 Treatment naïve, usually 24 weeks Relapse, partial response, null response  Genotype 4 Treatment naïve, 48 weeks Relapse, partial response, null responder *Those not treatment naïve, treated on a case by case basis.

14. TREATMENT  Monitoring Ultrasound every 6 months CBC, CMP, PT/INR, AFP every 6 months EGD or ESO cam to check for varices at least once Education Liver biopsy? Every patient gets treatment, not every patient is a candidate for antiviral treatment

15. TREATMENT  Antiviral Treatment Goal is achieving SVR Ask ‘when’ not ‘if’ a candidate for treatment No marijuana or other illicit drug use Abstinence from ETOH for at least 3 months HCV PCR (viral load) Depression screening before and during treatment Liver biopsy if not already done for GT 1 Education class to review expectations of frequent visits, labs and possible side effects.

16. STANDARD ANTIVIRAL THERAPY  Pegylated interferon therapy (PegIFN) Pegasys PegIntron Injections one time per week, duration based on genotype and response Must be kept cool (in the fridge!) Can be taken alone, although sustained viral response is diminished.  Ribavirin Tablets taken every day, dose based on genotype Not used as monotherapy

17. DIRECT ACTING ANTIVIRAL/ PROTEASE INHIBITOR  ONLY GT 1 PATIENTS ARE CANDIDATES  NO PRESCRIPTIONS TO BE FILLED WITHOUT FIRST CHECKING WITH PROVIDER WHO IS TREATING THE HEPATITIS C.  MULTIPLE SIDE EFFECTS AND DRUG INTERACTIONS.

18. DIRECT ACTING ANTIVIRAL/ PROTEASE INHIBITOR BOCEPREVIR/VICTRELIS ○ Treatment naïve Lead in phase 4 weeks, response guided therapy, generally 28 weeks of triple therapy ○ Relapse, partial responder, null responder Lead in phase 4 weeks, response guided therapy, 36-48 weeks of triple therapy

19. DIRECT ACTING ANTIVIRAL/ PROTEASE INHIBITOR TELAPREVIR/INCIVEK ○ Treatment naïve No lead in phase Triple therapy for 12 weeks RGT—generally done in 24 weeks ○ Relapse, partial responder, null responder No lead in phase Triple therapy for 12 weeks RGT-completed in 36-48 weeks

20. SIDE EFFECTS  Multiple side effects that can be mild to severe  Flu like symptoms, depression, dry skin, insomnia, hair loss, increased pain  Flu like symptoms most common  Will make autoimmune disorders worse i.e. Psoriasis—needs Derm monitoring  Depression: increased risk for suicidal ideation, worsening anxiety etc

21. ADDITIONAL SIDE EFFECTS WITH USE OF DAA/PI  Profound anemia  Increased risk of neutropenia  Increased risk of significant rash  Ano-rectal pain  Dysguesia  **this is NOT intended to be a complete list, see prescribing information for these medications.

22. APPROPRIATE CODING EIA RESULT PCR RESULT RIBA RESULT HEP C STATUS ICD-9 CODE NEG (w/o Tx) NEGNegative, not exposed to HCV NONE NEG (w/o Tx) POSPreviously exposed to Hep C, at time of testing, not chronically infected V01.79 POSNEG (w/o Tx) NEGFalse positive Ab-not exposed NONE

23. APPROPRIATE CODING EIA RESULT PCR RESULT RIBA RESULT HEP C STATUS ICD-9 CODE POSNEG (w/o Tx) POS Previously exposed to hepatitis C, at time of testing, not chronically infected V01.9 ANYNEG WITH TX ANYCleared virus in response to treatment 070 series ANYPOSANYChronic Hepatitis C 070 series NONE UNKNOWNIf test ordered: V73.9 Counseling: V65.49

24. RESOURCES  Several websites www.hepatitis.va.gov www.hepatitiscnewdrugs.blogspot.com www.aasld.org  Hepatitis C Resource Centers (HCRC) www.hepatitis.va.gov  Support Groups

25. CASE STUDY # 1  48 yo african american male with Hepatitis C type 1a, previously treated with peginterfon and ribavirin in 2009, relapsed within 3 months of stopping therapy, HCV PCR 500,000, PLT count 120, Albumin 3.2. Previous history of IVDU, marijuana, and ETOH use. Has been clean and sober for the last 5 years.

26. CASE STUDY #1 cont.  What treatment options would you discuss with him? A. None—it is more likely he would not respond to treatment and the risks/benefits are too great. B. Liver biopsy and consider treatment to include a direct acting antiviral. C. Retreatment with standard therapy and continue for 72 weeks

27. ??QUESTIONS??