Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg-IFNα-2a/RBV combination therapy in Azerbaijani patients
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Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease throughout the world. The presence of mutations in different regions of the HCV subtype 1b (HCV-1b) nonstructural 5A (NS5A) gene may be associated with response to interferon therapy. This study evaluated whether amino acid substitutions in the NS5A protein of HCV-1b correlated with response to pegylated interferon alfa-2a (peg-IFNα-2a) and ribavirin (RBV) combination therapy in Azerbaijani patients. From March 2010 to April 2014, a total of 34 chronically HCV-1b-infected Azerbaijani patients were enrolled in this prospective study. After extraction of RNA from plasma specimens, the entire sequences of the NS5A gene of HCV was amplified by reverse transcription nested polymerase chain reaction (RT-nested PCR), and the PCR products were sequenced subsequently. The data that were obtained revealed that there was no correlation between the response to HCV combination therapy and the number of mutations in the NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 regions of HCV. It also was found that changes from isoleucine to valine (I2252 V), aspartic acid to glutamic acid (D2257), arginine to lysine (R2269 K), and arginine to glycine in NS5A-PKRBD and from glycine to glutamic acid (G2379E) in the NS5A-V3 region were not associated with HCV treatment outcome. This study showed that genetic variability in the NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 regions is not a predictive factor of SVR, NR or relapse in HCV genotype1b treated with peg-IFNα-2a/RBV combination therapy.
KeywordsSustained Virological Response NS5A Protein NS5A Region Cobas Amplicor Monitor Reverse Transcription Nest Polymerase Chain
This study was supported by Research Deputy of Iran University of Medical Sciences, grant number 15927.
Conflict of interest
The authors have no conflict(s) of interest.
- 6.Bokharaei-Salim F, Keyvani H, Monavari SH, Alavian SM, Fakhim S, Nasseri S (2013) Distribution of Hepatitis C Virus Genotypes among Azerbaijani Patients in Capital City of Iran-Tehran. Hepat Mon 13(9):e13699Google Scholar
- 7.Yen YH, Hung CH, Hu TH, Chen CH, Wu CM, Wang JH et al (2008) Mutations in the interferon sensitivity-determining region (nonstructural 5A amino acid 2209-2248) in patients with hepatitis C-1b infection and correlating response to combined therapy of pegylated interferon and ribavirin. Aliment Pharmacol Ther 27(1):72–79PubMedCrossRefGoogle Scholar
- 10.Chayama K, Tsubota A, Kobayashi M, Okamoto K, Hashimoto M, Miyano Y et al (1997) Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection. Hepatology 25(3):745–749PubMedCrossRefGoogle Scholar
- 26.Munoz de Rueda P, Casado J, Paton R, Quintero D, Palacios A, Gila A et al (2008) Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 of hepatitis C virus genotype 1 and their relationships to pegylated interferon-ribavirin treatment responses. J Virol 82(13):6644–6653PubMedCrossRefGoogle Scholar
- 31.Kmieciak D, Kruszyna L, Migdalski P, Lacinski M, Juszczyk J, Trzeciak WH (2006) Mutations within protein kinase R-binding domain of NS5A protein of hepatitis C virus (HCV) and specificity of HCV antibodies in pretreatment sera of HCV-chronically infected patients and their effect on the result of treatment. Jpn J Infect Dis 59(2):92–99PubMedGoogle Scholar
- 35.Sarrazin C, Berg T, Lee JH, Teuber G, Dietrich CF, Roth WK et al (1999) Improved correlation between multiple mutations within the NS5A region and virological response in European patients chronically infected with hepatitis C virus type 1b undergoing combination therapy. J Hepatol 30(6):1004–1013PubMedCrossRefGoogle Scholar
- 37.Kumthip K, Pantip C, Chusri P, Thongsawat S, O’Brien A, Nelson KE et al (2011) Correlation between mutations in the core and NS5A genes of hepatitis C virus genotypes 1a, 1b, 3a, 3b, 6f and the response to pegylated interferon and ribavirin combination therapy. J Viral Hepat 18(4):e117–e125PubMedCrossRefGoogle Scholar