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Viral Hepatitis

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Hepatitis C Quicknotes

for Health Care Providers

Hepatitis C Quicknotes

Screening and Testing

Whom To Test
  1. Patients wanting to be tested.
  2. Patients having one or more of the following risk factors:
    • Vietnam-era Veteran
    • Transfusions before 1992
    • Intravenous drug use
    • Exposure of skin to blood
    • Multiple sex partners
    • Hemodialysis
    • Tattoos/Piercings
    • Nasal cocaine use
    • Unexplained liver disease
    • Unexplained abnormal ALT
    • Heavy alcohol use
Initial Testing

  1. Anti-HCV by ELISA
  2. AST/ALT (if not done previously)

Pretest Counseling
  1. For risk behaviors
  2. Limitations of ELISA test
  3. Schedule test and follow-up visit

Posttest Strategy

Result of Anti-HCV by ELISA
  • Negative
    • Patient is unlikely to be infected with HCV unless immunocompromised
    • If suspicion is high (patient has risk factors and is immunocompromised or patient has risk factors and acute hepatitis), obtain HCV RNA by PCR
  • Indeterminate
    • Uncertain whether patient is infected with HCV (could be in the process of forming antibodies, or other factors unrelated to HCV are present)
    • Obtain HCV RNA by PCR
  • Positive
    • Patient may be infected with HCV; test does not indicate whether infection is acute, chronic, resolved; result may be false positive
    • Get HCV RNA by PCR; positive result confirms that patient has active HCV.

Antiviral Treatment Eligibility

Candidates for Antiviral Treatment
  1. All patients with positive HCV RNA are potential candidates
  2. Treatment should be offered to patients with liver histology showing more than portal fibrosis (including those with compensated cirrhosis) and to those without contraindications

Antiviral Treatment Eligibility

Contraindications
  1. Interferon (if contraindicated, patient should not receive any therapy since ribavirin alone is not useful)
    • Platelet count ≤70,000 cells/µL
    • ANC ≤1,500 cells/µL
    • Life-determining extrahepatic disease (malignancy, unstable angina, severe COPD)
    • Clinically decompensated liver disease
    • Uncontrolled autoimmune disorders
    • Pregnancy or planned pregnancy in patient or partner, or unwillingness to use birth control
    • Documented nonadherence to prior therapy, or failure to complete pretreatment evaluation appointments or procedures
    • Inability to self-administer or to arrange administration of parenteral medication
    • Severe uncontrolled psychiatric disease, particularly depression with current suicidal risk
    • Ongoing injection drug use
    • Ongoing alcohol abuse
  2. Ribavirin (if contraindicated, interferon monotherapy can be considered)
    • Serum creatinine ≥1.5 g/dL or creatinine clearance ≤50 ml/min
    • Hemoglobin <12 g/dL in men or <11 g/dL in women
    • Thalassemia or other hemoglobinopathy
    • Significant cardiac disease (arrhythmias, angina, CABG, MI) in past 12 months
    • Pregnancy or planned pregnancy in patient or partner, or unwillingness to use birth control

Antiviral Treatment Eligibility

Pretreatment Assessment
  1. Necessary Evaluations
    • Medical history
    • Psychiatric history
    • Screening for depression and alcohol use
    • Biochemical markers of liver injury and synthetic dysfunction
      • Serum ALT
      • Serum albumin
      • Serum bilirubin (particularly direct)
      • Prothrombin time
    • Hemoglobin, hematocrit, total WBC, WBC with differential and platelet count
    • Thyroid function tests
    • Serum creatinine
    • Serum glucose or HgbA1C in diabetic patients
    • Pregnancy test (in women of child-bearing potential)
    • HIV serology
    • Serum HBsAg, anti-HBs, anti-HBc (total) and anti-HAV (total)
    • Quantitative HCV RNA
    • HCV genotype
    • Previous antiviral therapies and response
    • ECG in preexisting cardiac disease
  2. Highly recommended evaluations
    • Liver biopsy to stage severity of disease (especially in patients with genotype 1 infection)
    • Eye examination for retinopathy in patients with diabetes or hypertension
    • Serum ferritin, iron saturation and serum ANA
    • Urine toxicity screen for opiates, cocaine, and amphetamines

Antiviral Treatment Eligibility

Pretreatment Counseling
  1. Cessation of alcohol use
  2. Likelihood of achieving SVR
  3. Side effects of therapy
  4. Interferon
    • Flulike symptoms
    • Bone marrow suppression (greater with peginterferon)
    • Aggravation of autoimmune disorders
    • Neuropsychiatric symptoms
    • Seizures
    • Acute cardiac and renal failure
    • Retinopathy
    • Interstitial pulmonary fibrosis
  5. Ribavirin
    • Hemolytic anemia
    • Significant teratogen
    • Rashes
    • Headaches
    • Shortness of breath
    • GI effects
  6. Contraception
    • Adequate contraception needed during treatment and for 6 months after completion of treatment
  7. Importance of adherence

Antiviral Treatment Strategy

Genotype 1
  1. Peginterferon alfa 2a (Pegasys) 180 mcg SC once weekly (regardless of weight) OR
  2. Peginterferon alfa 2b (PEG-Intron) 1.5 mcg/kg SC once weekly up to 150 mcg/week (see chart below) AND
  3. PEG-IFN alfa 2b Dosing
    WT (lbs)Vial Size (µg/0.5mL)PEG dose (mL)
    <88500.5
    88-110800.4
    111-141800.5
    142-1661200.4
    167-1871200.5
    >1871500.5
  4. Ribavirin (Rebetol, Copegus)
  5. RIBAVIRIN DOSE
    WT (lbs)Total Daily DosageDosing Schedule
    ≤1651,000 mg QD2 (200 mg) tablets PO morning
    3 (200 mg) tablets PO evening
    >1651,200 mg QD3 (200 mg) tablets PO BID
  6. Duration of therapy
    • If 4-week HCV RNA undetectable (RVR), 24 weeks may be sufficient
    • If no RVR, but 12-week HCV RNA undetectable or decreased by >2 log 10 (EVR), 48 weeks is sufficient
    • If no RVR or EVR, extending duration to 72 weeks may be beneficial if HCV RNA undetectable at week 24 (if patient has advanced fibrosis and depending on tolerance of therapy)

Antiviral TX Strategy

Genotype 2-3
  1. Peginterferon alfa 2a (Pegasys) 180 mcg SC once weekly (regardless of weight) OR
  2. Peginterferon alfa 2b (PEG-Intron) 1.5 mcg/kg SC once weekly OR
  3. PEG-IFN alfa 2b Dosing
    WT (lbs)PEG vial to use (ug/0.5mL)PEG dose (mL)
    <88500.5
    88-110800.4
    111-141800.5
    142-1661200.4
    167-1871200.5
    >1871500.5
  4. Ribavirin 800 mg QD (400 mg PO BID)
  5. Duration of therapy
    • Standard treatment of duration is 24 weeks
    • For patients with low pretreatment HCV RNA (<600,000 IU/mL) who are not tolerating therapy, 16 weeks of treatment may be sufficient
    • For patients with genotype 3 and high viral load (>600,000) IU/mL) or steatosis, treatment beyond 24 weeks may improve response

Antiviral TX Strategy

Follow-Up Lab Monitoring
  1. Hgb, Hct, and WBC with differential and platelet count, creatinine
    • At week 1 or 2, at week 4, then every 1-2 months
  2. Serum ALT
    • At month 1, then every 1-2 months
  3. Pregnancy test
    • Monthly during therapy and for 6 months after completing therapy
  4. TSH
    • At least every 12 weeks during therapy
  5. Blood glucose
    • At least every 12 weeks during therapy
  6. HCV RNA by quantitative and/or qualitative assay
    • At week 4, 12, and 24 during therapy, at end of therapy, and 6 months after completion of therapy

Antiviral TX Strategy

Rules For Adjusting Therapy According To CBC Changes
  1. Hgb 10-11 g/dL
    • Peginterferon.
      • Do not modify dosage
    • Ribavirin
      • If no or minimal symptoms, do not modify dosage
      • If symptomatic, decrease by 200 mg/day and/or consider erythropoietin, particularly if cirrhotic, posttransplant, or HIV/HCV coinfected
    • Candidates for Recombinant Erythropoietin Criteria for Use for Hepatitis C Treatment-Related Anemia
      • Rule out other causes of anemia
      • Anemia persists at 2 weeks after reducing ribavirin
      • No hypertension
    • Dosage:
      • Epoetin alfa 40,000 units SC/week
      • Darbepoetin alfa 200 mcg SC every other week
    • Goal:
      • Hemoglobin 12 g/dL
  2. Hgb 8.5-10 g/dL
    • Peginterferon
      • Do not modify dosage
    • Ribavirin
    • Candidates for erythropoietin
      • Rule out other causes of anemia
      • Anemia persists at 2 weeks after reducing ribavirin
      • No hypertension
    • Dosage:
      • Epoetin alfa 40,000 units SC weekly
      • Darbepoetin alfa 200 mcg SC every other week
    • Goal:
      • Hemoglobin 12 g/dL
  3. Hgb <8.5 g/dL
    • Peginterferon.
      • Do not modify dosage
    • Ribavirin
      • Discontinue until resolution
  4. WBC <1,500
    • Peginterferon alfa 2b
      • Reduce dosage by 50% and reevaluate
    • Ribavirin
      • Do not modify dosage
  5. WBC <1,000
    • Peginterferon alfa 2b
      • Discontinue until resolution
    • Ribavirin
      • Do not modify dosage
  6. ANC <750
    • Peginterferon
      • Reduce peginterferon alfa 2a dosage to 135 mcg/wekk and reevaluate
      • Reduce peginterferon alfa 2b dosage by 50% and reevaluate
    • Ribavirin
      • Do not modify dosage
  7. ANC <500
    • Peginterferon
      • Discontinue until resolution
    • Ribavirin
      • Do not modify dosage
    • Consider G-CSF in patients who are cirrhotic, posttransplant, or HIV/HCV coinfected, particularly if neutropenia persists despite peginterferon dosage reduction
  8. Platelets <80,000
    • Peginterferon
      • Reduce peginterferon alfa 2b dosage by 50% and reevaluate
    • Ribavirin
      • Do not modify dosage
  9. Platelets <50,000
    • Peginterferon
      • Reduce peginterferon alfa 2a dosage to 90 mcg/week and reevaluate
      • Discontinue peginterferon alfa 2b until resolution
    • Ribavirin
      • Do not modify dosage
  10. Platelets <25,000
    • Peginterferon
      • Discontinue until resolution
    • Ribavirin
      • Do not modify dosage

Endpoints of HCV Therapy

  1. RVR:
    • HCV RNA <50 IU/mL at week 4 into treatment
  2. EVR:
    • >2 log 10 reduction from baseline HCV RNA at week 12 of treatment
  3. ETR:
    • Undetectable HCV RNA at completion of treatment
  4. SVR:
    • Undetectable HCV RNA at week 24 after completion of treatment
  5. Relapse:
    • Undetectable viremia during or at the end of treatment but HCV RNA is detectable after treatment is stopped
  6. Nonresponse:
    • Detectable HCV RNA throughout treatment