The role of interferon in the new era of hepatitis C treatments

Abstract

Interferon has been the backbone of HCV treatment since this agent was first introduced nearly two decades ago. Interferon acts to eradicate HCV via two mechanisms: by directly inhibiting HCV replication via an indirect anti-viral mechanism and by modulating an immune response against hepatocytes infected with HCV. The current treatment of chronic HCV genotype 1 is the combination of peginterferon, ribavirin and a single direct acting anti-viral agent (DAA). Within the next 1–2 years multiple DAA combinations will eradicate and cure HCV at high rates without interferon. The role interferon will play in the next era of HCV treatment will depend upon balancing cost, efficacy and the development of an interferon with a more favorable adverse event profile.

Keywords::

• chronic hepatitis C virus
• IL28B
• interferon
• response-guided therapy

Financial & competing interests disclosure

M Shiffman has received consulting fees from Abbvie, Achillion, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Gen-Probe, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Roche/Genentech and Vertex; grant support from Abbvie, Achillion, Beckman-Colter, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Globeimmune, Intercept, Lumena and Novartis; and speaker fees from Bayer, Gilead, GlaxoSmithKline, Janssen, Merck, Roche/Genentech and Vertex. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Two forms of type I IFN, IFN-α types 2a and 2b, are currently utilized to treat chronic hepatitis C virus (HCV). IFN-λ has recently been shown to be highly effective in suppressing HCV, and the limited receptor distribution for this type III IFN appears to be associated with less flu-like symptoms, bone marrow suppression and psychiatric side events.

• The single most important factor affecting the slopes of viral decay during treatment with peginterferon appears to be the host gene IL-28B.

• The higher rates of sustained virologic response (SVR) observed in patients of Asian descent and the lower rates of SVR observed in African Americans compared with Caucasians are directly related to the frequency of the IL28B CC genotype in these racial and ethnic populations.

• Response-guided therapy dictates that patients who become HCV RNA undetectable rapidly after the onset of treatment can achieve maximal SVR rates even with a shortened duration of therapy.

• Peginterferon and RBV therapy are associated with significant side effects, which preclude up to 15% of patients from completing therapy. Triple therapy with the use of telaprevir and boceprevir potentiates these adverse events. Both telaprevir and boceprevir suppress the bone marrow and lead to more severe anemia than is observed with peginterferon and ribavirin.

• Sofosbuvir and ribavirin are now approved for use as the first IFN-free treatment for patients with HCV genotypes 2 and 3. In patients with genotype 2, SVR rates exceed 90% with just 12 weeks of treatment regardless of the degree of fibrosis.

• IFN, with its unique mechanism of action, may still be required in those few patients who cannot be cured by antiviral agents alone.