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 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<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. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.