25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end

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Chronic hepatitis caused by infection with hepatitis C virus C (HCV) (therefore known as chronic hepatitis C (CHC)) is a leading cause of liver disease worldwide. For the past 25 years, recombinant interferon-α (IFNα) has been the main component of treatments for HCV infection. Treatment efficacy has shown a stepwise improvement following the pegylation of IFNα and its use in combination with other antiviral drugs. However, viral escape mechanisms, refractory IFNα signalling in the liver and substantial drug toxicity still limit the efficacy of this treatment. A new generation of HCV-specific antiviral drugs will probably improve response rates and might replace IFNs in CHC treatment in the next few years. This Timeline article summarizes the history of CHC treatment using recombinant IFNα with an emphasis on the mechanisms of action and the causes of non-response.

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Figure 1: Natural history of CHC.
Figure 2
Figure 3: Virological responses following CHC treatment with pegIFNα and ribavirin.
Figure 4: The stepwise increase in sustained virological response rates in the past 25 years.
Figure 5: Host and viral factors that regulate endogenous ISG expression in the liver of patients with CHC.


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Heim, M. 25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end. Nat Rev Immunol 13, 535–542 (2013) doi:10.1038/nri3463

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