The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients.
BACKGROUND
The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries.


OBJECTIVE
The aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients.


METHODS
A total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay.


RESULTS
In this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006).


CONCLUSIONS
The data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in Azerbaijani patients with chronic hepatitis C. Moreover, host genetic polymorphisms, such as those of the IL28B locus, might be useful for predicting the responsiveness to Peg-IFNα-2a/RBV combination therapy against HCV.
Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran; HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, IR Iran.
Farah
F
Bokharaei-Salim
Department of Arboviruses and Viral Hemorrhagic Fevers (National Ref Lab), Pasteur Institute of Iran, Tehran, IR Iran.
Mostafa
M
Salehi-Vaziri
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, IR Iran.
Farzin
F
Sadeghi
Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran.
Maryam
M
Esghaei
Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran.
Seyed Hamidreza
SH
Monavari
Middle East Liver Disease Center, Tehran, IR Iran; Iran Hepatitis Network, Tehran, IR Iran.
Seyed Moayed
SM
Alavian
Department of Civil Engineering, Faculty of Engineering, Payame Noor University, Karaj, IR Iran.
Shahin
S
Fakhim
Department of Virology, Iran University of Medical Sciences, Tehran, IR Iran.
Hossein
H
Keyvani
Core Protein; Hepatitis C Virus; IL28B; Pegylated Interferon; Polymorphisms; Ribavirin