ORIGINAL ARTICLE Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg-IFNa-2a/RBV combination therapy in Azerbaijani patients Farah Bokharaei-Salim • Hossein Keyvani • Mostafa Salehi-Vaziri • Farzin Sadeghi • Seyed Hamidreza Monavari • Leila Mehrnoush • Seyed Moayed Alavian Received: 11 January 2014 / Accepted: 26 May 2014 Ó Springer-Verlag Wien 2014 Abstract 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-IFNa-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 pro- spective 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-IFNa-2a/RBV com- bination therapy. Introduction Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease in different parts of the world [1, 2]. Pegylated interferon alfa-2a (Peg-IFNa-2a) in combination with ribavirin (RBV) is a standard treatment regimen for chronic HCV infection. However, this treatment leads to a response rates between 48 % and 88 % with different HCV genotypes [3, 4]. Different parameters have been shown to predict the response to antiviral therapy, of which the HCV genotype and the genetic heterogeneity of the virus have great importance. Generally individuals infected with HCV genotypes 2 and 3 have better response than those infected with HCV genotype 1 [5]. The predominant HCV genotype in Azerbaijani patients chronically infected with HCV is subtype 1b (71.1 %), followed by subtype 3a (17.0 %), genotype 2 (6.8 %), mixed infection (3.4 %), and subtype 1a (1.7 %) [6]. It is thought that both host (e.g., innate immunity and genetic variation in IL28b) and viral factors (e.g., the HCV genotype) affect the sensitivity or resistance to antiviral therapy [7]. F. Bokharaei-Salim Á H. Keyvani (&) Department of Virology, Iran University of Medical Sciences, Tehran, Iran e-mail: keyvanlab@yahoo.com M. Salehi-Vaziri Á F. Sadeghi Department of Virology, Tehran University of Medical Sciences, Tehran, Iran S. H. Monavari Departments of Virology and Anti Microbial Resistant Research Center, Iran University of Medical Sciences, Tehran, Iran L. Mehrnoush Á S. M. Alavian Middle East Liver Disease Center, Tehran, Islamic Republic of Iran L. Mehrnoush Á S. M. Alavian Iran Hepatitis Network, Tehran, Iran 123 Arch Virol DOI 10.1007/s00705-014-2133-0