Abstract
A first-generation protease inhibitor (PI) against HCV non-structural 3/4A serine protease was approved worldwide at the end of 2011. We are now facing a revolutionary change in therapeutic strategies for chronic HCV infection, from interferon (IFN)-based therapies to direct-acting antivirals (DAAs). The efficacy of antiviral therapy varies with HCV genotype. The most intractable and most common HCV worldwide is HCV genotype 1 (G1). Viral and host factors participating in the virological outcome of IFN-based therapy have been extensively examined. However, in the era of DAAs, the significance of these factors will gradually decrease. Instead, viral factors related to resistance against DAAs are becoming the main focus. In this review, the viral factors participating in the response to IFN-based therapies are summarized, and the issue of viral resistance to DAAs is discussed.
Highlights
The last decade has been the era of pegylated-interferon (PEGIFN) plus ribavirin (RBV) combination therapy for chronic HCV infection
These findings suggested that core 70/91, substitution at 70, is a key factor for predicting therapeutic efficacy in HCV G1b, regardless of geographic differences and irrespective of genetic variations in IL28B
These factors may be still important in the early stages of direct-acting antivirals (DAAs)-based therapy, because the efficacy of this type of therapy depends largely on susceptibility to PEG-IFN and RBV
Summary
The last decade has been the era of pegylated-interferon (PEGIFN) plus ribavirin (RBV) combination therapy for chronic HCV infection. At the end of 2011, first-generation nonstructural 3/4A (NS3/4A) serine protease inhibitors (PIs), such as teraprevir [1] and boceprevir [2], were approved for the treatment of chronic HCV genotype 1 (G1) infection, and triple therapy with PEG-IFN and RBV was widely introduced worldwide. In the era of PEG-IFN plus RBV therapy, the issue of emerging resistant virus was not generally taken into consideration [7]. This issue will be the focus of much attention in the early stages of the DAA era [8,9]. Viral factors that may be related to DAAbased anti-viral therapy are discussed
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