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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.
Abstract:
Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations. Clearly this problem may impair success of eradication strategies. With this background, several questions marks still exist around HCV treatment, including whether pan-genotypic treatments with complete effectiveness in any clinical conditions really exist outside clinical trials, the actual cost-effectiveness of genotyping testing, and utility of RAS detection in viral quasispecies by next generation sequencing approach. In this review, we describe these critical points by discussing recent literature data and our research experience.
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