title: IL28Bgenotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study.
abstract: OBJECTIVE
  Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships betweenIL28Brs12979860 genotype and liver fibrosis stage in CHC patients.
  
  
  METHODS
  A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records.
  
  
  RESULTS
  2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution ofIL28Bgenotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number ofIL28BT alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups.IL28Bgenotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection.
  
  
  CONCLUSIONS
  This large, international study found thatIL28Brs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East.
authors.affiliation: Liver Unit, IRCCS Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, 71013 Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Hepatology Unit, Hôpital Haut-Lévêque, CHU Bordeaux, 33600 Pessac, France.
authors.forename: Victor
authors.initials: V
authors.lastname: De Ledinghen
authors.affiliation: Hepatology Unit, Groupe Hospitalier Nord, CHU Lyon, 69004 Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Bailly
authors.affiliation: Gastroenterology Department, University of Chile Clinical Hospital, Santiago, 8380456 Chile.
authors.forename: Javier
authors.initials: J
authors.lastname: Brahm
authors.affiliation: Latvian Centre of Infectious Diseases, LLC Riga East University Hospital, Riga, 1006 Latvia.
authors.forename: Jazeps
authors.initials: J
authors.lastname: Keiss
authors.affiliation: Centre of Hepatology, Gastroenterology and Dietetics, Vilnius University, 08661 Vilnius, Lithuania.
authors.forename: Jonas
authors.initials: J
authors.lastname: Valantinas
authors.affiliation: Center for Infectious Diseases, West Tallinn Central Hospital, 10617 Tallinn, Estonia.
authors.forename: Nele
authors.initials: N
authors.lastname: Rasmann
authors.affiliation: Biostatistics, PROMETRIS GmbH, 68219 Mannheim, Germany.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.affiliation: Global Medical Affairs, F. Hoffmann-La Roche Ltd, 4074 Basel, Switzerland ; AbbVie, North Chicago, IL USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Tatsch
authors.affiliation: Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, 4074 Basel, Switzerland.
authors.forename: Georgios
authors.initials: G
authors.lastname: Bakalos
authors.affiliation: Institute of Cellular and Molecular Sciences, Queen Mary University of London, London, E1 2AT UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
keywords: Advanced fibrosis; Chronic hepatitis C; Gen-C study; Hepatitis C; IL28B