Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment
To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. Sequences within HCV NS5A [PKR binding domain (PKRBD) and...
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Published in | World journal of gastroenterology : WJG Vol. 23; no. 25; pp. 4538 - 4547 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Abstract | To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.
Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed
direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α),
= 49; IFN-α + ribavirin (RBV),
= 75; pegylated (peg) IFN-α + RBV,
= 47; first-generation direct-acting antivirals (DAAs),
= 13; and second-generation DAAs,
= 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR).
For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR
NVR; PKRBD: 5.82 ± 3
4.86 ± 2 mutations,
= 0.045; ISDR: 2.65 ± 2
1.51 ± 1.7 mutations,
= 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD,
= 0.02; ISDR,
= 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (
= 0.001).
The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL. |
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AbstractList | To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.
Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed
direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α),
= 49; IFN-α + ribavirin (RBV),
= 75; pegylated (peg) IFN-α + RBV,
= 47; first-generation direct-acting antivirals (DAAs),
= 13; and second-generation DAAs,
= 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR).
For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR
NVR; PKRBD: 5.82 ± 3
4.86 ± 2 mutations,
= 0.045; ISDR: 2.65 ± 2
1.51 ± 1.7 mutations,
= 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD,
= 0.02; ISDR,
= 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (
= 0.001).
The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL. |
Author | Gila Medina, Ana Casado Ruíz, Jorge Ruíz Extremera, Angeles Muñoz de Rueda, Paloma Salmerón, Javier Fuentes Rodríguez, José Manuel Quiles Pérez, Rosa Martín Álvarez, Ana Belén |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28740342$$D View this record in MEDLINE/PubMed |
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Copyright | The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. 2017 |
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Keywords | Interferon-based therapy Sustained virological response Chronic hepatitis C Number of mutations NS5A region Interferon-free therapy |
Language | English |
License | This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
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Notes | Author contributions: Salmerón J contributed to planning and conducting the study and collecting and interpreting the data; Muñoz de Rueda P, Fuentes Rodríguez JM and Quiles Pérez R contributed to collecting and interpreting the data and drafting the manuscript; Gila Medina A, Martín Álvarez AB, Casado Ruíz J and Ruíz Extremera Á contributed to collecting the data; and Muñoz de Rueda P contributed to the biostatistical analysis. Supported by “Consejería de Salud de la Junta de Andalucía”, No. PI0137/07; and “Instituto de Salud Carlos III”, No. FIS-Intrasalud PI010/717. Telephone: +34-95-8023655 Fax: +34-95-8023434 Correspondence to: Dr. Rosa Quiles Pérez, CIBERehd Researcher, Research Support Unit, University Hospital San Cecilio of Granada, Dr/ Olóriz 16, 18012 Granada, Spain. rosa-quiles@hotmail.com |
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SubjectTerms | Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Basic Study Drug Resistance, Multiple, Viral - genetics Drug Therapy, Combination Female Genotype Hepacivirus - genetics Hepacivirus - isolation & purification Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - virology Humans Interferon-alpha - pharmacology Interferon-alpha - therapeutic use Male Mutation Polyethylene Glycols - pharmacology Polyethylene Glycols - therapeutic use Prospective Studies Retrospective Studies Ribavirin - pharmacology Ribavirin - therapeutic use Sequence Analysis, RNA Sustained Virologic Response Viral Load - drug effects Viral Nonstructural Proteins - genetics |
Title | Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment |
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