abc’s of hepatitis c treatment readiness and follow-up geri hirsch rn-np nurse practitioner...

ABC’s Of Hepatitis C Treatment Readiness and

Follow-up Geri Hirsch RN-NP

Nurse Practitioner Hepatology

[email protected]

mailto:[email protected]

Overview of Presentation

• HCV screening/testing

• Pretreatment counseling

• Encouraging adherence

• Managing adverse events

Screening

(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

(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


(2) Anyone with CLINICAL CLUES suspicious for hepatitis C infection (and

above risk factors)

• 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


Hepatitis C Treatment

Medication HCV Genotypes 1 or 4 HCV Genotypes 2 or 3

PegIFN alfa-2a[1] 180 μg/wk SQ (hemodialysis: reduce to 135 μg/wk SQ)

• Ribavirin[2] 200 mg tablets in 2 divided doses/day

• 1000 mg/day (< 75 kg)• 1200 mg/day (≥ 75 kg)

• 800 mg/day

PegIFN alfa-2b[3] 1.5 μg/kg/wk SQ (If CrCl 30-50 mL/min: reduce dose by 25%;if CrCl 10-29 mL/min: reduce dose by 50%)

• Ribavirin[4] 200 mg capsules in 2 divided doses/day

• ≤ 65 kg: 800 mg/day• 66-80 kg: 1000 mg/day• > 80-105 kg: 1200 mg/day• > 105 kg: 1400 mg/day

• ≤ 65 kg: 800 mg/day• 66-80 kg: 1000 mg/day• > 80-105 kg: 1200 mg/day• > 105 kg: 1400 mg/day

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.

HCV Standard of Care Therapy: Dosing Recommendations

HCV Genotype and Response

0

10

20

30

40

50

60

70

80

90

Geno 1 Geno 2+3 Geno1 Geno 2+3

24 wksRBV800mg/day+pegIFN alfa2a

24 wks of RBV 1000/1200mg/day +pegIFN alfa 2a

48 wksRBV800mg/day+pegIFN alfa2a

48 wks of RBV 1000/1200mg/day +pegIFN alfa 2a

Advanced Fibrosis Minimal Fibrosis

Hadziyannis SJ, et al. Ann Intern Med. 2004;140:346-355.

SV

R (

%)

Current and Future Treatments

0

10

20

30

40

50

60

70

80

SV

R (

%)

Current treatment

Future treatment

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.

Naïve non responders Naïve non responders

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)

Response Definitions in Patients

Receiving HCV Therapy

Response definitions Time Point HCV RNA Level

Rapid virologic response - RVR

4 wks into therapy Undetectable

Early virologic response - EVR

12 wks into therapy Undetectable (complete)≥ 2 log decrease from baseline (partial)

End of treatment response - EOT

End of therapy Undetectable

Sustained virologic response - SVR

6 mos post therapy Undetectable

Ghany MG, et al. Hepatology. 2009;49:1335-1374.

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

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

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

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

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

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

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.

Encouraging Adherence

Adherence to PegIFN/RBV

• 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

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.

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.

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.

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

Managing Adverse Events

PegIFN Adverse EventsAE Occurring in > 20% of Pts, %

PegIFN alfa-2a/RBV (n = 1035)

PegIFN alfa-2b/RBV (n = 1019)

Fatigue/insomnia 64/41 67/38

Headache 41 50

Nausea 34 40

Anemia 34 35

Rash 34 29

Neutropenia 31 26

Irritability/depression 25/20 25/25

Chills 23 39

Injection-site reactions 23 34

Myalgia/arthralgia 22/22 27/21

Dyspnea 22 21

Pyrexia 21 35

Anorexia 21 29

Alopecia 17 23

Peginterferon alfa-2b [package insert]. 2010.

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.

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.

Adverse Event Potential Interventions

Flulike symptoms (fever, chills, HA, myalgias, arthralgias, fatigue)

• Acetaminophen (≤ 2 grams/day) *• Bed rest• Fluids (noncaffeinated) 8-10 glasses/day

Fatigue • Administer IFN at bedtime• Low-impact exercise• Short naps, adjust work schedule• Assess for anemia, TSH..

Mood changes (depression, suicidal/ homicidal tendencies, anxiety, irritability)

• Avoid stimulants like caffeine, Ck TSH • Antidepressants (eg, SSRI), psych referral*• Short-acting benzodiazepines may help

Insomnia • Develop good sleep patterns *• Limit fluid intake/caffeine before bedtime• Consider sleep aids (eg, diphenhydramine,

trazodone, zolpidem)

Supportive Therapy for HCV Treatment-Related Adverse Events

Adverse Event Potential Interventions

Nausea/vomiting/anorexia • Take RBV with food• Eat 6-8 small meals per day• Ginger may help: tea, ale, syrup• Carbonated fluids, jello drinks• Provide prophylactic antiemetics (eg, prochlorperazine)

Diarrhea • Drink noncaffeinated fluids • Increase fiber in diet (cereal, toast, rice), BRAT diet• Avoid foods that are spicy, greasy, acidic• Consider antidiarrheals or psyllium

Skin irritation (injection-site reactions, dry skin, rashes)

• Rotate injection sites• Take cool baths and use moisturizing soaps• Consider topical steroid cream or oral antihistamines

Hair loss/thinning Education, wigs; reversible/temporary as hair grows back

Supportive Therapy for HCV Treatment-Related Adverse Events

RBV-Induced Anemia

• 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

1. Ribavirin tablets [package insert]. 2010. 2. Ribavirin capsules [package insert]. 2010. 3. Sulkowski MS, et al. Gastroenterology. 2010;139:1602-1611.

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

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.



• 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


• 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)


Canadian Consensus Guidelines-Management of Hepatitis C , 2007

Nursing Role in Patient Education and HCV Drug Therapy Management

Patient Education Drug Therapy Management

Anticipated benefits and risks of treatment

Baseline assessment for contraindications to therapy

Lifestyle changes Injection training and/or administration of injections

Anticipated treatment duration/FU and need for adherence


Prevention of disease progression•Avoid hepatotoxins—Acetaminophen, alcohol, herbals, NSAIDs•Vaccine advocates—hepatitis A and B, influenza, pneumococcal

Assessment and evaluation of adherence

Reduce risk of HCV transmission Management of treatment toxicity

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.

Success is dependent on effort and teamwork .

abc’s of hepatitis c treatment readiness and follow-up geri hirsch rn-np nurse practitioner...

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