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Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection

Julia Dietz1,2, Olga V Kalinina3,4, Johannes Vermehren1,2

  • 1Department of Internal 1, University Hospital, Goethe University, Frankfurt, Germany.

Journal of Viral Hepatitis
|May 13, 2020
PubMed

Insights

Hepatitis C virus (HCV) genotype 4 subtype 4r shows more resistance-associated substitutions (RASs) than other subtypes. Retreatment with direct-acting antivirals (DAAs) is highly effective, achieving high sustained virologic response (SVR) rates across all subtypes.

Area of Science:

  • Hepatology
  • Virology
  • Infectious Diseases

Background:

  • Direct-acting antivirals (DAAs) have transformed Hepatitis C Virus (HCV) treatment.
  • Data on resistance-associated substitutions (RASs) in European HCV genotype 4 patients are limited.
  • Understanding RASs is crucial for optimizing DAA retreatment strategies.

Purpose of the Study:

  • To investigate the prevalence of RASs in HCV genotype 4 subtypes before and after DAA failure.
  • To evaluate the efficacy of retreatment in patients experiencing DAA failure.
  • To identify specific RASs associated with DAA failure in different genotype 4 subtypes.

Main Methods:

  • Analysis of NS3, NS5A, and NS5B RASs in 195 European patients with HCV genotype 4.
  • Retrospective analysis of retreatment outcomes in patients who experienced DAA failure.
  • Comparison of RAS prevalence between DAA-naïve patients and those with DAA failure.

Main Results:

  • HCV genotype 4 subtype 4r showed a significantly higher prevalence of NS5A RASs compared to subtypes 4a and 4d.
  • Specific RASs (L28V, L30R, M31L) were common in subtype 4r and persisted after NS5A inhibitor failure.
  • Retreatment regimens achieved high sustained virologic response (SVR) rates (≥90%) across all subtypes and prior treatment failures.

Conclusions:

  • HCV genotype 4 subtype 4r harbors a greater burden of RASs, particularly within the NS5A region.
  • Resistance-guided retreatment strategies using first- and second-generation DAAs are highly effective.
  • High SVR rates (≥90%) can be achieved in patients with DAA failure, regardless of subtype or initial regimen.
Keywords:
DAA failureHCV genotype 4hepatitis C virusresistance-associated substitutionsretreatment

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