Hepatitis C Organism-Specific Therapy 

The primary goal of therapy is viral eradication. Secondary goals of therapy include reduction of symptoms and prevention or delay of progression to cirrhosis or hepatocellular carcinoma (HCC).^[1] The duration of therapy is determined by the hepatitis C virus (HCV) genotype and the virologic response to therapy. The quantitative HCV ribonucleic acid (RNA) level is used to assess response to therapy and as a guide to discontinuation of treatment.

Institution of therapy for hepatitis C is rarely an emergency, except in some cases of severely symptomatic HCV-induced cryoglobulinemic vasculitis; other treatments (eg, plasmapheresis) may be instituted before contemplating interferon.^[1] Treatment is contraindicated in women who are or may become pregnant and in men whose female partner is pregnant; this is on account of the potential teratogenicity of ribavirin.

Sustained virologic response (SVR) is defined as the absence of detectable HCV RNA on blood testing 6 months after the completion of antiviral therapy; SVR can be equated with cure. Follow-up includes HCV viral load testing at weeks 4, 8, 12, and 24, and then every 3 months.^{[1, 2, 3, 4, 5]}

Peginterferon- and ribavirin-based treatment recommendations for patients with genotype 1 or 4

• Peginterferon alfa-2a 180µg SC once weekly plus  ribavirin 1000-1200mg PO daily (< 75kg, give 400mg in AM, 600mg in PM; ≥75kg, give 600mg BID)^[6] or
• Peginterferon alfa-2b 1.5µg/kg/wk SC plus  ribavirin 800-1400mg PO daily in divided doses (≤65kg, give 400mg BID; 66-85kg, give 400mg in AM, 600mg in PM; 86-105kg, give 600mg BID; >105kg, give 600mg in AM, 800mg in PM)^[7]
• Duration of therapy: 48wk for HCV genotype 1 or 4

Protease inhibitor ̶ based treatment recommendations for patients with genotype 1

The HCV protease inhibitors boceprevir and telaprevir received FDA approval in May 2011 for use in combination with peginterferon and ribavirin in patients with genotype 1 infections.

Boceprevir-based therapy should be stopped if the HCV RNA is ≥ 100 IU/mL at treatment week 12 or if HCV RNA is detectable at treatment week 24.

Telaprevir-based therapy should be stopped if the HCV RNA is >1000 IU/mL at treatment week 4 or treatment week 12 or if the HCV RNA is detectable at treatment week 24.

Boceprevir-based regimens for previously untreated patients with genotype 1:

• Patients receive a lead-in of dual therapy with peginterferon alfa-2a 180µg SC once weekly plus  ribavirin 1000-1200mg PO daily (< 75kg, give 400mg in AM, 600mg in PM; ≥75 kg, give 600mg BID) or
• Peginterferon alfa-2b 1.5µg/kg/wk SC plus ribavirin 800-1400mg PO daily in divided doses (≤65kg, give 400mg BID; 66-85kg, give 400mg in AM, 600mg in PM; 86-105kg, give 600mg BID; >105kg, give 600mg in AM, 800mg in PM) for treatment weeks 1 through 4
• After week 4, add boceprevir 800mg PO TID with a meal or light snack (continue same doses of peginterferon and ribavirin)
• If patients have an undetectable HCV RNA level at treatment weeks 8 and 24, continue peginterferon/ribavirin/boceprevir (same doses) through treatment week 28
• If patients have a detectable HCV RNA level at treatment week 8 and an undetectable HCV RNA at treatment week 24, continue peginterferon/ribavirin/boceprevir (same doses) through treatment week 36, then an additional 12wk of peginterferon/ribavirin (same doses) to complete 48wk of therapy
• Patients with compensated cirrhosis receive 4wk of peginterferon/ribavirin (same doses), followed by 44wk of peginterferon/ribavirin/boceprevir (same doses)^[2]

Telaprevir-based regimens for previously untreated patients with genotype 1:

• Triple therapy with peginterferon alfa-2a 180µg SC once weekly plus  ribavirin 1000-1200mg PO daily (< 75kg, give 400mg in AM, 600mg in PM; ≥75kg, give 600mg BID) plus  telaprevir 750mg PO TID with food (employed for 12wk), followed by dual therapy with peginterferon/ribavirin (same doses) or
• Peginterferon alfa-2b 1.5µg/kg/wk SC plus  ribavirin 800-1400mg PO daily in divided doses (≤65kg, give 400mg BID; 66-85kg, give 400mg in AM, 600mg in PM; 86-105kg, give 600mg BID; >105kg, give 600mg in AM, 800mg in PM) plus telaprevir 750mg PO TID with food (employed for 12wk), followed by dual therapy with peginterferon/ribavirin (same doses)
• If patients have an undetectable HCV RNA level at treatment weeks 4 and 12, continue peginterferon/ribavirin (same doses) for an additional 12wk
• If patients have a detectable HCV RNA level (1000 IU/mL or less) at treatment weeks 4 and/or 12, continue peginterferon/ribavirin (same doses) for an additional 36wk

Second-line protease inhibitor ̶ based treatments

Boceprevir-based regimens for previously treated patients with genotype 1:

• Patients receive a lead-in of dual therapy with peginterferon alfa-2a 180µg SC once weekly plus  ribavirin 1000-1200mg PO daily (< 75kg, give 400mg in AM, 600mg in PM; ≥75kg, give 600mg BID) or
• Peginterferon alfa-2b 1.5 µg/kg/wk SC plus ribavirin 800-1400mg PO daily in divided doses (≤65kg, give 400mg BID; 66-85kg, give 400mg in AM, 600mg in PM; 86-105kg, give 600mg BID; >105kg, give 600mg in AM, 800mg in PM) for treatment weeks 1 through 4
• After week 4, add boceprevir 800mg PO TID with a meal or light snack (continue same doses of peginterferon and ribavirin)
• If patients have an undetectable HCV RNA level at treatment weeks 8 and 24, continue peginterferon/ribavirin/boceprevir (same doses) through treatment week 36
• If patients have a detectable HCV RNA level at treatment week 8 and an undetectable HCV RNA at treatment week 24, continue triple therapy with peginterferon/ribavirin/boceprevir (same doses) through treatment week 36, then an additional 12wk of peginterferon/ribavirin (same doses) to complete 48wk of therapy
• Patients with compensated cirrhosis receive 4wk of peginterferon/ribavirin (same doses), followed by 44wk of peginterferon/ribavirin/boceprevir (same doses)^[2]

Telaprevir-based regimens for previously treated patients with genotype 1:

• Triple therapy with peginterferon alfa-2a 180µg SC once weekly plus  ribavirin 1000-1200mg PO daily (< 75kg, give 400mg in AM, 600mg in PM; ≥75kg, give 600mg BID) plus  telaprevir 750mg PO TID with food (employed for 12wk), followed by dual therapy with peginterferon/ribavirin (same doses) for 36 additional weeks or
• Peginterferon alfa-2b 1.5 µg/kg/wk SC plus ribavirin 800-1400mg PO daily in divided doses (≤65kg, give 400mg BID; 66-85kg, give 400mg in AM , 600mg in PM; 86-105 kg, give 600mg BID; >105 kg, give 600mg in AM, 800mg in PM) plus telaprevir 750mg PO TID with food (employed for 12wk), followed by dual therapy with peginterferon/ribavirin (same doses) for 36 additional weeks

Treatment recommendations for patients with chronic hepatitis C genotypes 2 and 3

• Peginterferon alfa-2a 180µg SC once weekly plus  ribavirin 400mg PO BID^[6] or
• Peginterferon alfa-2b 1.5µg/kg/wk SC plus  ribavirin 400mg PO BID^[7]
• Duration of therapy: 24wk for HCV genotype 2 or 3

Dosage adjustments of peginterferon therapy in patients with renal insufficiency

Peginterferon alfa-2a:

• Creatinine clearance (CrCl) < 50 mL/min: Caution advised
• End-stage renal disease on hemodialysis: Decrease dose to 135µg SC once weekly

Peginterferon alfa-2b:

• CrCl 30-50mL/min: Reduce dose by 25%
• CrCl < 30mL/min: Reduce dose by 50%^[7]

Note: Ribavirin should not be used in patients with CrCl < 50mL/min^[1]