, Volume 77, Issue 10, pp 1043–1055 | Cite as

Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use

  • Sabrina BagaglioEmail author
  • Caterina Uberti-Foppa
  • Giulia Morsica
Leading Article


Multiple direct-acting antiviral (DAA)-based regimens are currently approved that provide one or more interferon-free treatment options for hepatitis C virus (HCV) genotypes (G) 1–6. The choice of a DAA regimen, duration of therapy, and use of ribavirin depends on multiple viral and host factors, including HCV genotype, the detection of resistance-associated amino acid (aa) substitutions (RASs), prior treatment experience, and presence of cirrhosis. In regard to viral factors that may guide the treatment choice, the most important is the infecting genotype because a number of DAAs are genotype-designed. The potency and the genetic barrier may also impact the choice of treatment. One important and debated possible virologic factor that may negatively influence the response to DAAs is the presence of baseline RASs. Baseline resistance testing is currently not routinely considered or recommended for initiating HCV treatment, due to the overall high response rates (sustained virological response >90%) obtained. Exceptions are patients infected by HCV G1a when initiating treatment with simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in sites of resistance. On the basis of these observations, first-line strategies should be optimized to overcome treatment failure due to HCV resistance.


Sustain Virological Response Virologic Failure Sustain Virological Response Rate Sofosbuvir Genetic Barrier 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

Conflict of Interest

SB, CUF, and GM declare that they have no conflict of interest.


No funding was used in the preparation of this manuscript.


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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Division of Infectious Diseases IRCCS Ospedale San RaffaeleMilanItaly

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