ABC’s Of Hepatitis C Treatment Readiness and Follow-up

1. ABC’s Of Hepatitis C Treatment Readiness and Follow-up Geri Hirsch RN-NP Nurse Practitioner Hepatology geri.hirsch@cdha.nshealth.ca

2. Overview of Presentation • HCV screening/testing • Pretreatment counseling • Encouraging adherence • Managing adverse events

3. Screening

5. (1) Anyone with RISK BEHAVIOURS/POTENTIAL EXPOSURES to HCV • High Risk • Injection drug use (IDU) • Incarceration • Born, traveled, or resided in a region in which HCV infection is more common • Receipt of health care where there is a lack of universal precautions (nosocomial transmission) • Blood transfusion, blood products, or organ transplant before 1992 in Canada http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf

6. (1) Anyone with RISK BEHAVIOURS/POTENTIAL EXPOSURES to HCV • Intermediate Risk • Hemodialysis • Infant born to mother with HCV infection • Needle stick injuries • Other Risks Associated With HCV EXPOSURE • Sharing sharp instruments/personal hygiene materials • with HCV+ person (e.g., razors, scissors, nail clippers, toothbrush) • Tattooing, body piercing, scarification, female genital mutilation or other ceremonial rituals • Intranasal (snorting) & inhalation drug use • Homelessness, residency in group homes or shelters • Higher-risk sexual behaviour http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf

7. Abnormal liver biochemistry (e.g., ALT) Drug and/or alcohol dependency (past or present) Blood diseases requiring multiple transfusions of blood products (e.g., hemophilia, thalassemia, sickle cell anemia) HBV infection HIV infection Signs of chronic liver disease (e.g., hepatomegaly +/- splenomegaly, spider nevi, palmar erythema, jaundice) Vasculitis (due to associated cryoglobulinemia) History of unexplained renal impairment Non-Hodgkin’s lymphoma (2) Anyone with CLINICAL CLUES suspicious for hepatitis C infection (and above risk factors) http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf

8. Hepatitis C Treatment

9. HCV Standard of Care Therapy: Dosing Recommendations 1. Peginterferon alfa-2a [package insert]. 2010. 2. Ribavirin tablets [package insert]. 2010. 3. Peginterferon alfa-2b [package insert]. 2010. 4. Ribavirin capsules [package insert]. 2010.

10. HCV Genotype and Response SVR (%) Advanced Fibrosis Minimal Fibrosis Hadziyannis SJ, et al. Ann Intern Med. 2004;140:346-355.

11. Current and Future Treatments Future treatment Current treatment SVR (%) Naïve non responders Naïve non responders 1. Poordad F, et al. AASLD 2010. Abstract LB-4. 2. Jacobson IM, et al. AASLD 2010. Abstract 211. 3. Bacon BR, et al. AASLD 2010. Abstract 216. 4. These data are available in press release format only, have not been peer reviewed, may be incomplete, and we await presentation or publication in a peer-reviewed format before conclusions should be made from these data.

12. Predictors of Treatment Response Patient Factors • Age • Sex • Race • Weight • Insulin resistance • Fatty liver disease • Mental health • Drug/alcohol use • Cirrhosis • HIV coinfection • IL28B status Virus Factors • Genotype • HCV RNA level Regimen Factors • Adherence to pegIFN/RBV • Weight-based RBV dosing (genotypes 1/4) • Reported improved response rates with protease inhibitors (in the future, for genotype 1 patients only)

13. Response Definitions in Patients Receiving HCV Therapy Ghany MG, et al. Hepatology. 2009;49:1335-1374.

14. Preparing the Patient for HCV Therapy • Provide and verify patient’s/family’s understanding of basic information about • HCV transmission, • prognosis, • treatment, • adverse event management • Obtain and discuss • patient’s /family’s willingness • adherence to medications • need for visits/lab follow-ups

15. Preparing the Patient for HCV Therapy • Social assessment • housing, • disability, • social supports, • transportation, finances, drug plan • Educate • alcohol, herbals, • hepatotoxins, • safe injection techniques* • Ensure immunizations for HAV, HBV, pneumococcal, and seasonal influenza

16. Preparing the Patient for HCV Therapy • Cautionary Uses • Cardiovascular disease • Autoimmune disease • Cryoglobulinemia related symptoms • Psychiatry history/suicide • Alcohols and substance misue • Other • DM,seziure disorder,decomplenstated liver disease ,renal diseasem lung disease, retinopathy, hemoglobinopathies

17. Preparing the Patient for HCV Therapy • Provide and verify patient’s understanding of basic information of side effect management • Encourage patient’s/family’s active participation in treatment decisions and ability to ask questions • Review laboratory parameters and urine pregnancy test* • Serum ALT, AST, bilirubin, alkaline phosphatase, albumin, serum creatinine / BUN, TSH, glucose, urinalysis • prothrombin time/INR,CBC with differential and platelet count,HIV and hepatitis B surface antigen • ANA*,genotype, viral load**,occular exam* • weight

18. Preparing the Patient for HCV Therapy • Additional Tests • Chest x ray, PA and LAT • Cardiac assessment - EKG and in consultations with MD consider a cardiology consult • Mental Health Assessment • Abdominal ultrasound • Iron saturations (and hemochromatosis gene test if indicated • Serum cooper, ceruloplasmin, and alpha 1 if indicated

19. Preparing the Patient for HCV Therapy • Assure effective contraception and reinforce issue of contraception • Administer/demonstrate techniques for pegIFN injections • Provide information on safe disposal of needles

20. PegIFN Administration • PegIFN alfa-2a[1] • Premixed vials/prefilled syringes • Dose is not weight adjusted: 180 μg SQ every wk • Syringes are overfilled; ensure correct dose before administration • PegIFN alfa-2b[2] • Vials/syringes need to be reconstituted before use • Redipen • Weight-adjusted dose: 1.5 μg/kg per dose every wk • Allow to come to room temperature before use 1. Peginterferon alfa-2a [package insert]. 2010. 2. Peginterferon alfa-2b [package insert]. 2010.

21. Encouraging Adherence

22. Adherence to PegIFN/RBV 1. Mitra D, et al. Value Health. 2010;13:479-486. 2. McHutchison JG, et al. Gastroenterology. 2002;123:1061-1069. 3. Raptopoulou M, et al. J Viral Hepat. 2005;12:91-95. 4. Smith SR, et al. Ann Pharmacother. 2007;41:1116-1123. • Not all patients take al their medication. • In one US study 60% were adherent [1] • 80/80/80 phenomenon • taking > 80 % of medications correlates with SVR[2,3] • Remember patients may overestimate adherence [4] • For some individuals a multidisciplinary team may be beneficial for adherence

23. Major Predictors of Poor Adherence to Medication Patient and Treatment Factors • Treatment of asymptomatic disease • Presence of psychological comorbidities, especially depression • Patient’s lack of belief in treatment benefit • Treatment complexity • Adverse events of medication Other Factors • Poor relationship between the patient and provider • Inadequate follow-up or discharge preparation • Missed appointments • Cost of copayment, medication, or both Osterberg L, et al. N Engl J Med. 2005;353:487-497.

24. Strategies for Improving Adherence to a Medication Regimen • Identify risk factors for poor adherence early • Look for strategies to mitigate some of the factors • Emphasize value of regimen and potential results to pts • Some patients are asymptomatic • Provide simple, clear instructions and simplified regimen • Encourage the use of medication-dispensing packaging • Blister packs may be helpful Osterberg L, et al. N Engl J Med. 2005;353:487-497.

25. Strategies for Improving Adherence to a Medication Regimen • Customize regimen to pt lifestyle when possible • Injection days – weekend • Support from family members, friends, and community • Consider more “forgiving” medications • Medications with long half-lives, sustained release, or depot

26. Managing Adverse Events

27. PegIFN Adverse Events Peginterferon alfa-2b [package insert]. 2010.

28. RBV Adverse Effects • Adverse events occurring more frequently when RBV added to pegIFN vs pegIFN alone • Hemolytic anemia • Headache • Cough/SOB • Gastrointestinal upset • Rash • Insomnia • Teratogenicity Peginterferon alfa-2b [package insert]. 2010. Peginterferon alfa-2a [package insert]. 2010.

29. Adverse Event Management • Anticipate adverse events • Common and occur in nearly all patients • Severity and nature of toxicity is highly variable • If events are not managed well result …Negative impact on treatment outcome and quality of life • Adverse event management starts before treatment begins • Preemptive measures • Chronic health conditions are stable • Assess chronic health conditions to ensure they will not be significantly impacted with treatment side effects • Provide supportive care during therapy • During current treatment with pegIFN/RBV[1] • 10% to 14% of patients discontinue treatment due to adverse event • Monitor closely since fatalities can occur 1. Seeff LB, et al. Semin Liver Dis. 2010;30:348-360.

30. Supportive Therapy for HCV Treatment-Related Adverse Events

31. Supportive Therapy for HCV Treatment-Related Adverse Events

32. RBV-Induced Anemia 1. Ribavirin tablets [package insert]. 2010. 2. Ribavirin capsules [package insert]. 2010. 3. Sulkowski MS, et al. Gastroenterology. 2010;139:1602-1611. • RBV-induced anemia correlates with achieving RVR/SVR • Mean maximum Hb decrease of 2.9-3.1 g/dL in first 6-8 wks[1,2] • Occurs early within first 1-2 wks and remains low • Anemia during the first 4-8 wks associated with improved probability of achieving RVR and/or SVR[3] • Can worsen fatigue, SOB, CV, quality of life, and lead to discontinuation of treatment • Follow product monograph for dose modification

33. Managing Hematologic Adverse Events • Anemia • Specific thresholds for considering RBV dose reduction, discontinuation, and/or EPO * • Note FDA warnings regarding risks associated with ESAs • Neutropenia • Specific thresholds for considering pegIFN dose reduction, therapy discontinuation, and/or G-CSF* • Thrombocytopenia • Specific thresholds for considering pegIFN dose reduction, therapy discontinuation See package inserts for details

34. Laboratory monitoring for efficacy and treatment toxicity • Patients on PEG-Interferon combination therapy should have: • hematology and blood chemistry testing before the start of treatment and then periodically thereafter. • In the clinical trials CBC (including hemoglobin, neutrophil and platelet counts) and chemistries (including AST, ALT, bilirubin, and uric acid) were measured during the treatment period at weeks 2, 4, 8, 12, and then at 6-week intervals or more frequently if abnormalities developed. • TSH levels were measured every 12 weeks during the treatment period. See package inserts for details

35. Genotype non 2,3 HCV viral load baseline HCV viral load week 12 HCV RNA week 24 * HCV RNA week 48 HCV RNA week 72 Genotype non 2,3 HCV RNA baseline HCV RNA week 12 HCV RNA at the end of treatment* HCV RNA 24 week after completing treatment Laboratory monitoring for efficacy and treatment toxicity

36. Laboratory monitoring for efficacy and treatment toxicity • Patients on PEG-Interferon combination therapy should have: • HCV RNA/VL at baseline • HCV RNA VL at week 12 ( non genotype 2,3) • HCV PCR at week 12 (genotype 2 and 3) • HCV PCR at week 24 ( non genotype 2,3) • HCV PCR at week 24 ( non genotype 2,3) • HCV PCR at week 48( non genotype 2,3) • HCV PCR at week 48( non genotype 2,3) • HCV PCR at week 72 ( non genotype 2,3) See package inserts for details

37. Canadian Consensus Guidelines-Management of Hepatitis C , 2007

38. Canadian Consensus Guidelines-Management of Hepatitis C , 2007

39. Nursing Role in Patient Education and HCV Drug Therapy Management Marino EL, et al. J Manag Care Pharm. 2009;15:147-150. Smith JP, et al. Am J Health Syst Pharm. 2007;64:632-636.

40. Success is dependent on effort and teamwork .