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Upcoming direct acting antivirals for hepatitis C patients with a prior treatment failure

Tommaso Lorenzo Parigi1,2, Maria Corina Plaz Torres1, Alessio Aghemo1,2

  • 1Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, Italy.

Clinical and Molecular Hepatology
|May 3, 2019
PubMed

Insights

Hepatitis C virus (HCV) direct-acting antiviral (DAA) treatment failures occur in 1-3% of patients. This review explores advanced therapeutic strategies, including novel drug combinations, for patients with treatment failure and advanced liver disease.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacology

Background:

  • Direct-acting antivirals (DAAs) achieve high sustained virological response (SVR) rates for hepatitis C virus (HCV) infection.
  • A small percentage of patients (1-3%) do not achieve SVR after DAA treatment.
  • DAA failure is associated with advanced liver disease, specific HCV genotypes/subtypes, and resistance-associated substitutions.

Purpose of the Study:

  • To review current and emerging therapeutic strategies for patients who fail direct-acting antiviral therapy for hepatitis C virus.
  • To present the latest evidence on treatment options for difficult-to-treat patient populations.

Main Methods:

  • Review of clinical trial data.
  • Analysis of real-world evidence on DAA treatment strategies.
  • Examination of European Association for the Study of the Liver (EASL) guidelines.

Main Results:

  • The EASL guidelines recommend three options for DAA failures: sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks (90-99% effective), glecaprevir/pibrentasvir (GLE/PIB) for 12 weeks (90-97% effective) for those with failure predictors.
  • Prolonged treatment durations or combinations like SOF+GLE/PIB or SOF/VEL/VOX±ribavirin are theoretically beneficial for highly treatment-experienced patients, though lacking extensive published data.

Conclusions:

  • Effective treatment options exist for most DAA failures, including specific regimens recommended by EASL.
  • Further research and real-world data are needed to confirm the efficacy of prolonged or novel combination therapies for the most challenging HCV treatment failures.
Keywords:
AntiviralsHepatitis C virus (HCV)Re-treatmentSofosbuvir

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