title: Interleukin-28B rs12979860 C allele: Protective against  advanced fibrosis in chronic hepatitis C genotype  1 infection.
abstract: Background and Aim: While genetic polymorphisms upstream of the interleukin-28B(IL28B) gene are associated with necroinflammatory activity grade in chronic hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is less definitive. Pretreatment liver biopsies in a cohort of treatment-naïve patients with HCV-1 were analyzed to evaluate associations between liver histology, and the rs12979860 and rs8099917 IL28B single nucleotide polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high activity grade (A2/3) were identified using multivariable logistic regression analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141 patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P = 0.03), with an increasing number of Talleles associated with a higher frequency of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97–0.99; P < 0.0001), high activity grade (OR 5.68, 95% CI% 1.86–17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36, 95% CI 0.14–0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00–1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be independently associated with a lower prevalence of advanced fibrosis stage in HCV-1 infection. This association warrants further evaluation.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Kitson
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Reynold
authors.initials: R
authors.lastname: Leung
authors.forename: Peter
authors.initials: P
authors.lastname: Button
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: Darrell H G
authors.initials: DH
authors.lastname: Grawford
authors.forename: William
authors.initials: W
authors.lastname: Siebert
authors.forename: Martin D
authors.initials: MD
authors.lastname: Weltman
authors.forename: Wendy S C
authors.initials: WS
authors.lastname: Cheng
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D065840:Protective Factors; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda