Interleukin-28B rs12979860 C allele: protective against advanced fibrosis in chronic hepatitis C genotype 1 infection

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-naive 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 T alleles associated with a higher frequency of advanced fibrosis: CC 11.0 , CT 18.0 , TT 33.3 (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