Brief Article
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World J Gastroenterol. Jan 14, 2013; 19(2): 290-298
Published online Jan 14, 2013. doi: 10.3748/wjg.v19.i2.290
IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients
Mostafa K El Awady, Noha G Bader El Din, Ashraf Tabll, Yaser El Hosary, Ashraf O Abdel Aziz, Hesham El Khayat, Mohsen Salama, Tawfeek H Abdelhafez
Mostafa K El Awady, Noha G Bader El Din, Ashraf Tabll, Tawfeek H Abdelhafez, Department of Microbial Biotechnology, National Research Center, Cairo, Giza 12622, Egypt
Yaser El Hosary, Department of Internal Medicin, National Research Center, Cairo, Giza 12622, Egypt
Ashraf O Abdel Aziz, Department of Tropical Medicine, Cairo University, Giza 12622, Egypt
Hesham El Khayat, Theodor Bilharz Research Institute, Giza 12622, Egypt
Mohsen Salama, National Liver Institute, Shebeen El Kom 32512, Egypt
Author contributions: El Awady MK designed the experiment, designed the new primers, and wrote the manuscript; Bader El Din NG, performed research work (IL28 PCR, CMV PCR, HCV PCR), edited the manuscript and made the final revision; Tabll A helped in the manuscript writing; El Hosary Y, Abdet Aziz AO, El Khayat H, Salama M provided blood samples; Abdelhafez TH participated in designing the new primers, and performed research work (IL28 PCR).
Supported by Misr El-Khair Foundation, Cairo, Egypt
Correspondence to: Dr. Mostafa El Awady, PhD, Department of Microbial Biotechnology, National Research Center, El-Behooth Street 12622, Dokki, Cairo, Giza 12622, Egypt. mkawady@yahoo.com
Telephone: +20-12-3132640 Fax: +20-2-3370931
Received: January 14, 2012
Revised: April 28, 2012
Accepted: May 5, 2012
Published online: January 14, 2013
Abstract

AIM: To test whether the status of positive cytomegalovirus (CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers.

METHODS: This study included 166 chronic hepatitis C (CHC) patients who received combined interferon and ribavirin therapy for 48 wk, 84 spontaneous hepatitis C virus (HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA, and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls. Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism (SNP) and CMV DNA detection. A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer. Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism (RFLP) genotyping. The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction. The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed.

RESULTS: Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response (SVR) while the genotypes C/T and TT were associated with lower SVR rates, 50% and 48%, respectively. SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations. Genotype CC was associated with the response to interferon (P = 0.025). Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity. The majority of spontaneously cleared subjects (86%) were C/C, confirming its protective role. The C/T allele was present in 71% of CHC patients compared with 38% of controls, so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response. CMV reactivation occurred in 40% of CHC patients. Co-infection with CMV seriously diminished the response to interferon (IFN) therapy, with SVR rates in C/C genotypes 87.5% in CMV-negative patients and 12.5% in CMV-positive patients (P < 0.0001). SVR rates among C/T carriers were reduced to < 50% in patients with positive CMV DNA while the non-response rate doubled. These data indicate that a supplemental assay for CMV viremia adds to the prognostic value of IL28B genotyping.

CONCLUSION: The results suggest that both genetic (i.e., spontaneous) and therapeutic (IFN-based therapy) arms are complementary in the battle against HCV. CMV DNA testing may be of value to better predict the response to IFN, particularly in IL28B C/T carriers.

Keywords: Hepatitis C, Interleukin 28B, Genetic polymorphisms, Human cytomegalovirus, Spontaneous clearance