title: [IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection].
abstract: BACKGROUND
  In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest.
  
  
  OBJECTIVE
  The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated.
  
  
  METHODS
  Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24-72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes.
  
  
  RESULTS
  The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) CONCLUSIONS: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients.
authors.affiliation: Pécsi Tudományegyetem, Általános Orvostudományi Kar, Orvos- és Egészségtudományi Centrum I. Belgyógyászati Klinika. alajos.par@aok.pte.hu
authors.forename: Alajos
authors.initials: A
authors.lastname: Pár
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pár
authors.forename: István
authors.initials: I
authors.lastname: Tornai
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalay
authors.forename: Dalma
authors.initials: D
authors.lastname: Várszegi
authors.forename: Edit
authors.initials: E
authors.lastname: Fráter
authors.forename: Mária
authors.initials: M
authors.lastname: Papp
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lengyel
authors.forename: János
authors.initials: J
authors.lastname: Fehér
authors.forename: Márta
authors.initials: M
authors.lastname: Varga
authors.forename: Judit
authors.initials: J
authors.lastname: Gervain
authors.forename: János
authors.initials: J
authors.lastname: Schuller
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Nemes
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Péterfi
authors.forename: Anna
authors.initials: A
authors.lastname: Tusnádi
authors.forename: Béla
authors.initials: B
authors.lastname: Hunyady
authors.forename: Attila
authors.initials: A
authors.lastname: Haragh
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szinku
authors.forename: László
authors.initials: L
authors.lastname: Pálinkás
authors.forename: Tímea
authors.initials: T
authors.lastname: Berki
authors.forename: Aron
authors.initials: A
authors.lastname: Vincze
authors.forename: Péter
authors.initials: P
authors.lastname: Kisfali
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D020011:Protective Agents / Q000378:metabolism*; D012254:Ribavirin / Q000627:therapeutic use*; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D020011:Protective Agents; D012254:Ribavirin; D014157:Transcription Factors; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C118437:negative elongation factor