title: Epstein-Barr virus and Interleukin-28B polymorphism in the prediction of response to interferon therapy in hepatitis C patients.
abstract: OBJECTIVE
  In chronic hepatitis C virus (HCV), viral and host factors are known to be predictors for anti-viral therapy. IL-28B genotype strongly influences treatment outcome, while Epstein-Barr virus (EBV) co-infection could accelerate the course of chronic HCV infection. This study was conducted to assess whether EBV co-infection adds to the predictive value of IL-28B.
  
  
  METHODS
  A total of 105 patients with chronic HCV were classified according to their response to treatment into two groups: 38 sustained virological responders (SVRs) and 67 nonresponders (NRs). Collected sera at baseline and follow-up (FUP) were used for assessing EBV antibodies by enzyme-linked immunosorbent assay (ELISA) and the expression of EBV genes (BNLF-1, BZLF-1, and EBER-2) by polymerase chain reaction (PCR). Collected peripheral blood was used for detecting IL-28B rs.12979860 single-nucleotide polymorphism.
  
  
  RESULTS
  Regarding IL-28B genotype frequencies, a significant difference (p=0.003) was observed between SVRs (C/C=51.4%, C/T=48.6%, T/T=0%) and NRs (C/C=25%, C/T=55%, T/T=20%). On assessing EBV infection at baseline and FUP, it was found that 61% and 55% were positive, respectively, with no significant difference between SVRs and NRs. As for anti-viral capsid antigen (VCA) antibodies, the NRs had significantly higher baseline anti-VCA immunoglobulin M (IgM) levels than SVRs (p=0.01). While FUP anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG reported a significant decline within SVR patients (p=0.02), neither baseline nor FUP anti-VCA IgG levels showed a statistically significant viral response. Finally, on comparing EBV markers with CC versus CT and TT genotypes, it was found that FUP anti-VCA IgG levels were significantly increased in CC genotype (p=0.003).
  
  
  CONCLUSIONS
  Interleukin-28B polymorphism could be a possible predictor of response to pegylated interferon/ribavirin therapy (PEG-IFN/RBV). Furthermore, co-infection with EBV did not affect the response to IFN-based therapy in HCV-infected patients.
authors.affiliation: Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. Electronic address: ncizekri@yahoo.com.
authors.forename: Abdel-Rahman N
authors.initials: AR
authors.lastname: Zekri
authors.affiliation: Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Dina
authors.initials: D
authors.lastname: Abdullah
authors.affiliation: Biochemistry Department, Faculty of Science, Ainshams University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Osman
authors.affiliation: Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Mahmoud N
authors.initials: MN
authors.lastname: El-Rouby
authors.affiliation: Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Naglaa
authors.initials: N
authors.lastname: Zayed
authors.affiliation: Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Esmat
authors.affiliation: Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Elakel
authors.affiliation: Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Hanan Abdel
authors.initials: HA
authors.lastname: Hafez
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D036022:Capsid Proteins / Q000097:blood; D060085:Coinfection; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D015534:Trans-Activators / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000906:Antibodies; D000956:Antigens, Viral; D000998:Antiviral Agents; D036022:Capsid Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; D015534:Trans-Activators; C063676:BZLF1 protein, Herpesvirus 4, Human; C041788:Epstein-Barr viral capsid antigen; C106732:Epstein-Barr virus encoded RNA 2; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417029:EBV-encoded nuclear antigen 1
keywords: Co-infection; Epstein-Barr virus; HCV; Interleukin-28B; NR; SVR