Role of IL28B gene polymorphism and cell-mediated immunity in spontaneous resolution of acute hepatitis C

Abstract

Background. A single-nucleotide polymorphism (SNP; rs12979860) near the IL28B gene has been associated with spontaneous and treatment-induced hepatitis C virus clearance. We investigated predictors of spontaneous disease resolution in a cohort of patients with acute hepatitis C (AHC), analyzing epidemiological, clinical and virological parameters together with IL28B.rs12979860 genotypes and cell-mediated immunity (CMI).Methods. Fifty-six symptomatic AHC patients were enrolled and followed prospectively. CMI was measured in 31 patients at multiple time points by interferon-γ enzyme-linked immunospot assay and was correlated to the IL28B.rs12979860 SNP.Results. Eighteen patients had a self-limiting AHC that was associated with female sex (P =. 028), older age (P =. 018), alanine aminotransferase level >1000 U/L (P =. 027), total bilirubin level >7 mg/dL (P =. 036), and IL28B.rs12979860 genotype CC (P =. 030). In multivariate analysis, only CC genotype was independently associated with self-limiting AHC (odds ratio, 5.3; 95% confidence interval, 1.1-26.5). Patients with the CC genotype with self-limiting AHC had a stronger (P =. 02) and broader (P =. 013) CMI than patients with the CT genotype with chronically evolving AHC. In patients with chronically evolving disease, CC genotype was associated with a broader CMI compared to CT genotype (P =. 028). A negative CMI was more frequently associated with CT genotype among persistently infected patients (P =. 043) and with persistent infection among CT patients (P =. 033).Conclusions. Self-limiting AHC was independently associated with CC genotype. The correlation between IL28B.rs12979860 genotypes and CMI is suggestive of a possible important role of CMI in favoring hepatitis C virus clearance in CC patients. © 2013 The Author.