Hepatic C Treatment with Interferon and Ribavirin

Aka: Hepatic C Treatment with Interferon and Ribavirin

1. See Also
   1. Hepatitis C
2. Indications: Standard
   1. Serum ALT greater than twice normal (optional) and
   2. HCV RNA positive for >50 copies/ml and
   3. Liver biopsy positive (may not need if Genotype 2-3)
      1. Cirrhosis (if present clinically, biopsy not needed)
      2. Liver fibrosis: Scale of 0 (none) to 4 (severe)
      3. Liver inflammation: 0 (none) to 4 (Cirrhosis)
   4. Additional guidelines
      1. Liver biopsy with moderate to severe disease
      2. Regardless of AST or ALT values (may be normal)
      3. Ahmed (2004) Gastroenterology 126:1409-15
3. Contraindications
   1. Absolute Contraindications
      1. Allergy to Interferon or Ribavirin
      2. Decompensated Cirrhosis
      3. Pregnancy
      4. Ongoing intravenous Drug Abuse or Alcoholism
   2. Relative Contraindications
      1. Leukopenia
      2. Anemia
      3. Thrombocytopenia
      4. Some Autoimmune Conditions
      5. Coronary Artery Disease
      6. Uncontrolled mental health condition
4. Evaluation: Pre-treatment
   1. Complete history and physical for contraindications
   2. Laboratory testing as described in Hepatitis C
   3. Baseline labs for therapy - see monitoring below
5. Preparations: Interferon
   1. Pegylated Interferon alfa-2a (Pegasys)
      1. Adult Dose: 180 mcg SQ per week
   2. Pegylated Interferon alfa-2b (PEG-Intron)
      1. Adult Dose: 1.5 mcg/kg per week
   3. Interferon alfa-2b (Intron A)
      1. Pegylated Interferon is preferred (see above)
      2. Dose: 3 Million Units SQ three times per week
      3. Administer with Ribavirin if not contraindicated
      4. Cost: $8000 per 24 week course
      5. Rebetron combines Ribavirin and Interferon alfa-2b
6. Preparation: Ribavirin (if not contraindicated)
   1. Genotype 2 or 3 (all weights)
      1. Take 400 mg PO bid
   2. Genotype 1a, 1b and 4
      1. Weight >75 kg (165 lb): 600 mg PO bid
      2. Weight <75 kg (165 lb): 400 mg qAM, 600 mg qPM
7. Protocol
   1. Course
      1. Overall combined cost: $25,000 for 48 weeks
      2. Duration for up to 48 weeks
   2. Check Viral RNA load by PCR
   3. Initiate treatment at doses above
      1. Interferon
      2. Ribavirin
   4. Check Viral RNA load by PCR at 12 weeks
      1. Viral load High (<100 fold decrease)
         1. Stop treatment as unlikely to respond
      2. Viral load markedly lowered (>100 fold decrease)
         1. Continue antiviral course
   5. Antiviral Therapy Duration
      1. Genotype 1: 48 weeks
      2. Genotype 2 and 3: 24 weeks
   6. Check Viral RNA load by PCR at 24 weeks after therapy
      1. Virus detected: Relapse
      2. Virus not detected: 97% chance of cure
8. Monitoring
   1. Protocol
      1. Baseline labs
         1. Complete Blood Count (CBC) with platelets
         2. Urine Pregnancy Test
         3. Thyroid Stimulating Hormone (TSH)
         4. Liver Function Tests (AST, ALT, Bilirubin)
      2. Repeat labs at 2 weeks, 4 weeks and then monthly
         1. Complete Blood Count (CBC) with platelets
         2. Urine Pregnancy Test
         3. Liver Function Tests (AST, ALT, Bilirubin)
      3. Repeat TSH every 3 months
   2. Initial management of adverse blood counts
      1. Low Hemoglobin: Epogen 40,000 units SQ weekly
      2. Neutropenia: Consider G-CSF
   3. Response to labs refractory to Erythropoietin
      1. Indications to lower Ribavirin dose 200-400 mg/day
         1. Hemoglobin decreased <10 g/dl
         2. Hemoglobin drops >2 g/dl in one month if CAD
      2. Indications to lower PEG-Intron dose by 25-50%
         1. Hemoglobin drops >2 g/dl in one month if CAD
         2. WBC Count <1.5 x10^3/ul
         3. Neutrophil Count <0.75 x10^3/ul
         4. Platelet Count <50,000 to 80,000
      3. Indications to stop therapy
         1. Hemoglobin <8.5 g/dl
         2. Hemoglobin <12 g/dl after month on low dose if CAD
         3. WBC Count <1.0 x10^3/ul
         4. Neutrophil Count <0.5 x10^3/ul
         5. Platelet Count <25,000 to 50,000
9. Adverse Effects
   1. Anorexia or Nausea: Eat small, frequent meals
   2. Depression: Screen at baseline and every 3 months
   3. Fatigue: Regular mild Exercise
   4. Myalgia: Analgesics, Local Cold Therapy
   5. Cough: Usually self-limited; observe for pneumonitis
   6. Pruritus: See Pruritus Management
10. Efficacy
    1. HCV Genotype 1: 40-50% cure rate at 12 months
    2. HCV Genotype 2-4: 70-80% cure rate at 6 months
    3. Combined therapy is effective (even in relapse)
    4. Efficacy drops significantly with HIV coinfection
11. Nurse support lines for protocols (24 hour)
    1. Schering-Plough: 888-437-2608
    2. Roche Labs: 877-734-2797
12. References
    1. Fried (2002) N Engl J Med 347:975-82
    2. Kjaergard (2001) BMJ 323:1151-5
    3. Patel (2006) BMJ 332(7548): 1013-7
    4. Ward (2005) Am Fam Physician 72:655-62
    5. Wilkins (2010) Am Fam Physician 81(11): 1351-7