title: Role of IL28B gene polymorphism and cell-mediated immunity in spontaneous resolution of acute hepatitis C.
abstract: BACKGROUND
  A single-nucleotide polymorphism (SNP; rs12979860) near the IL28B gene has been associated with spontaneous and treatment-induced hepatitis C virus clearance. We investigated predictors of spontaneous disease resolution in a cohort of patients with acute hepatitis C (AHC), analyzing epidemiological, clinical and virological parameters together with IL28B.rs12979860 genotypes and cell-mediated immunity (CMI).
  
  
  METHODS
  Fifty-six symptomatic AHC patients were enrolled and followed prospectively. CMI was measured in 31 patients at multiple time points by interferon-γ enzyme-linked immunospot assay and was correlated to the IL28B.rs12979860 SNP.
  
  
  RESULTS
  Eighteen patients had a self-limiting AHC that was associated with female sex (P = .028), older age (P = .018), alanine aminotransferase level >1000 U/L (P = .027), total bilirubin level >7 mg/dL (P = .036), and IL28B.rs12979860 genotype CC (P = .030). In multivariate analysis, only CC genotype was independently associated with self-limiting AHC (odds ratio, 5.3; 95% confidence interval, 1.1-26.5). Patients with the CC genotype with self-limiting AHC had a stronger (P = .02) and broader (P = .013) CMI than patients with the CT genotype with chronically evolving AHC. In patients with chronically evolving disease, CC genotype was associated with a broader CMI compared to CT genotype (P = .028). A negative CMI was more frequently associated with CT genotype among persistently infected patients (P = .043) and with persistent infection among CT patients (P = .033).
  
  
  CONCLUSIONS
  . Self-limiting AHC was independently associated with CC genotype. The correlation between IL28B.rs12979860 genotypes and CMI is suggestive of a possible important role of CMI in favoring hepatitis C virus clearance in CC patients.
authors.affiliation: National Centre of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy. enea.spada@iss.it
authors.forename: Enea
authors.initials: E
authors.lastname: Spada
authors.forename: Pietro
authors.initials: P
authors.lastname: Amoroso
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.forename: Ornella
authors.initials: O
authors.lastname: Zuccaro
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Chiriacò
authors.forename: Patrizia
authors.initials: P
authors.lastname: Maio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maio
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Esposito
authors.forename: Corrado
authors.initials: C
authors.lastname: Mariano
authors.forename: Roberto
authors.initials: R
authors.lastname: Rinaldi
authors.forename: Pietro
authors.initials: P
authors.lastname: Bellissima
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Tosti
authors.forename: Paola
authors.initials: P
authors.lastname: Del Porto
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Francavilla
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mellace
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Garbuglia
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mele
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006526:Hepatitis C / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: acute hepatitis C; cell-mediated immunity; interleukin-28B; prognostic factors