Discussion on critical points for a tailored therapy to cure hepatitis C virus infection

Nadia Marascio1, Angela Quirino1, Giorgio Settimo Barreca1

  • 1Department of Health Sciences, Unit of Clinical Microbiology, Unit of Infectious and Tropical Diseases, Magna Graecia University, Catanzaro, Italy.

Insights

Hepatitis C virus (HCV) treatment is improving, but some patients still experience failure due to resistance. This review examines effective pan-genotypic treatments, genotyping costs, and resistance-associated substitutions detection for HCV eradication.

Area of Science:

  • Hepatology
  • Virology
  • Infectious Diseases

Background:

  • Hepatitis C virus (HCV) remains a significant global health concern, affecting millions worldwide.
  • Direct-acting antiviral (DAA) therapies since 2011 have transformed HCV treatment, improving sustained virological response (SVR) rates and enabling eradication strategies.
  • Treatment failures, though infrequent, can occur due to resistance-associated substitutions (RASs), which may be pre-existing or emerge during therapy, potentially hindering eradication efforts.

Purpose of the Study:

  • To critically evaluate the effectiveness of pan-genotypic HCV treatments in real-world clinical settings.
  • To assess the cost-effectiveness of HCV genotyping for guiding treatment decisions.
  • To determine the utility of detecting RASs in viral quasispecies using next-generation sequencing (NGS) for optimizing HCV treatment outcomes.

Main Methods:

  • Review of recent scientific literature on HCV treatment, resistance, and diagnostics.
  • Analysis of clinical data regarding the efficacy of direct-acting antiviral therapies.
  • Discussion of next-generation sequencing approaches for identifying resistance-associated substitutions in Hepatitis C virus populations.

Main Results:

  • While DAA therapies offer high SVR rates, questions persist regarding the universal effectiveness of pan-genotypic regimens outside controlled trials.
  • The cost-effectiveness of routine HCV genotyping for RAS detection requires careful consideration in clinical practice.
  • NGS offers a powerful tool for detecting minority RAS populations, but its clinical utility and integration into treatment strategies are still evolving.

Conclusions:

  • Further research is needed to confirm the real-world effectiveness of pan-genotypic HCV therapies across diverse patient populations and clinical scenarios.
  • Optimizing HCV eradication strategies requires a balanced approach to treatment selection, diagnostic testing, and resistance surveillance.
  • The integration of advanced molecular diagnostics like NGS may play a crucial role in overcoming treatment challenges and achieving global HCV elimination goals.

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