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Editorial
. 2018 Sep 27;10(9):543-548.
doi: 10.4254/wjh.v10.i9.543.

Hepatitis C resistance to NS5A inhibitors: Is it going to be a problem?

Heidar Sharafi  1 , Seyed Moayed Alavian  1
Affiliations
Editorial

Hepatitis C resistance to NS5A inhibitors: Is it going to be a problem?

Heidar Sharafi et al. World J Hepatol. .

Abstract

Treatment of hepatitis C virus (HCV) infection has evolved greatly through the recent decade. The availability of direct-acting antiviral agents (DAAs) targeting the functional proteins of HCV has resulted in the introduction of DAA-based combination therapies, providing an optimal rate of treatment success. Among the DAAs, NS5A inhibitors are used in most of the introduced and approved HCV antiviral regimens. Resistance-associated substitutions (RASs) are amino acid substitutions in HCV protein sequences that result in decreased antiviral efficacy of the HCV DAAs. Among the HCV RASs, the NS5A RASs were found to effectively modify and decrease treatment response to NS5A inhibitor-containing regimens. As a baseline predictor of treatment response, NS5A RAS draws attention for pretreatment testing in targeted patient groups. Given NS5A RASs are either naturally-occurring or DAA-selected, the application of NS5A RAS testing can be considered in two settings of NS5A inhibitor-naïve patients and NS5A inhibitor-experienced patients. Less than 5% of NS5A inhibitor-naïve patients harbor naturally-occurring NS5A RAS with high resistance level (> 100X resistance fold-change). In NS5A inhibitor-naïve patients, NS5A RAS testing accompanied by treatment optimization cannot increase treatment response more than 2%-3%, while in NS5A inhibitor-experienced patients, > 75% are found to have NS5A RASs > 100X and NS5A RAS testing in this group of patients seems to be reasonable. This editorial will address the debate on the application of NS5A RAS testing and will discuss if the NS5A RAS testing has any role in clinical management of hepatitis C.

Keywords: Direct-acting antiviral agent; Hepatitis C; NS5A; Resistance; Treatment.

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Conflict of interest statement

Conflict-of-interest statement: Both authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
NS5A resistance-associated substitution testing in NS5A inhibitor-naïve patients prior to treatment with NS5A inhibitor-containing regimen. A: Standard treatment strategy and outcome without NS5A resistance-associated substitution (RAS) testing; B: Optimized treatment strategy and outcome with NS5A RAS testing. The implementation of NS5A RAS testing is developed by decision-making based on the presence of RAS > 100X. SVR: Sustained virologic response.
Figure 2
Figure 2
NS5A resistance-associated substitution testing in NS5A inhibitor-experienced patients prior to retreatment with NS5A inhibitor-containing regimen. Optimized treatment strategy with NS5A resistance-associated substitutions (RAS) testing and the outcome is shown. The implementation of NS5A RAS testing is developed by decision-making based on the presence of RAS > 100X. SVR: Sustained virologic response.
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References

    1. Hesamizadeh K, Sharafi H, Rezaee-Zavareh MS, Behnava B, Alavian SM. Next Steps Toward Eradication of Hepatitis C in the Era of Direct Acting Antivirals. Hepat Mon. 2016;16:e37089. - PMC - PubMed
    1. Strader DB, Seeff LB. A brief history of the treatment of viral hepatitis C. Clin Liver Dis. 2012;1:6–11. - PMC - PubMed
    1. Behnava B, Sharafi H, Keshvari M, Pouryasin A, Mehrnoush L, Salimi S, Karimi Elizee P, Ghazimoghaddam M, Alavian SM. The Role of Polymorphisms Near the IL28B Gene on Response to Peg-Interferon and Ribavirin in Thalassemic Patients With Hepatitis C. Hepat Mon. 2016;16:e32703. - PMC - PubMed
    1. Alavian SM, Hajarizadeh B, Bagheri Lankarani K, Sharafi H, Ebrahimi Daryani N, Merat S, Mohraz M, Mardani M, Fattahi MR, Poustchi H, et al. Recommendations for the Clinical Management of Hepatitis C in Iran: A Consensus-Based National Guideline. Hepat Mon. 2016;16:e40959. - PMC - PubMed
    1. Sharafi H, Nikbin M, Alavian SH, Behnava B, Alavian SM. Efficacy and Safety of Generic Sofosbuvir/Ledipasvir Fixed-Dose Combination in Iranian Patients with Chronic Hepatitis C Virus Infection. Hepat Mon. 2017;17:e12216.

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