title: IL28B CC-genotype association with HLA-DQB1*0301 allele increases the prediction of spontaneous HCV RNA clearance in thalassaemic HCV-infected patients.
abstract: BACKGROUND
  A single nucleotide polymorphism (SNP), upstream of the IL28B gene has been recently associated with natural clearance of HCV. In a well-characterized cohort of patients with thalassaemia major exposed to the risk of acquiring HCV infection by blood transfusions, we aimed to replicate this finding and to evaluate whether combining the IL28B genotype and HLA class II alleles allow viral clearance to be accurately predicted.
  
  
  METHODS
  Of 168 patients, 130 with complete clinical history were included in the analysis. According with their HCV antibodies status 13 were defined HCV resistant, and 117 infected. Infected patients were subdivided, giving 49 with self-limiting and 68 with ongoing infection.
  
  
  RESULTS
  IL28B CC-genotype was observed in 32 patients with self-limiting and in 23 with ongoing infection (64% versus 34%; P=0.004). HLA DQB1*0301 allele was associated with viral clearance in 36 cases (73%; P<0.0001). Both DQB1*0301 and IL28B CC-genotype were found to be independent predictors of HCV clearance (OR=5.64, 95% CI 1.52-20.9 and OR=5.76, 95% CI 2.16-15.33, respectively). With the addition of DQB1*0301, the accuracy of the prediction increased from 63% to 69%.
  
  
  CONCLUSIONS
  In addition to IL28B CC-genotype, HLA DQB1*0301 helps in predicting natural clearance of HCV after acute infection.
authors.affiliation: Liver Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. a.mangia@tin.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Rosanna
authors.initials: R
authors.lastname: Santoro
authors.forename: Roberto
authors.initials: R
authors.lastname: Sarli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mottola
authors.forename: Valeria
authors.initials: V
authors.lastname: Piazzolla
authors.forename: Daniela
authors.initials: D
authors.lastname: Petruzzellis
authors.forename: Donato
authors.initials: D
authors.lastname: Bacca
authors.forename: Rocco
authors.initials: R
authors.lastname: Clemente
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Lazzaro
authors.initials: L
authors.lastname: di Mauro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lotti
authors.forename: Michele
authors.initials: M
authors.lastname: Sacco
authors.forename: Ippazio
authors.initials: I
authors.lastname: Stefano
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D060467:Disease Resistance; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D060005:Genotyping Techniques; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000502:physiology; D018937:Hepatitis C Antibodies / Q000032:analysis / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D007558:Italy; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood / Q000276:immunology; D065227:Transfusion Reaction; D019562:Viral Load / Q000276:immunology; D017086:beta-Thalassemia / Q000097:blood / Q000209:etiology / Q000821:virology*; D000095022:Interferon Lambda
chemical_list: D059866:HLA-DQ beta-Chains; D018937:Hepatitis C Antibodies; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C069051:HLA-DQB1 antigen; C000624353:interferon-lambda, human; D000095022:Interferon Lambda