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

Clin Infect Dis. 2013 Sep;57(6):803-11. doi: 10.1093/cid/cit402. Epub 2013 Jun 19.

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.

Keywords: acute hepatitis C; cell-mediated immunity; interleukin-28B; prognostic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Female
  • Hepatitis C / epidemiology
  • Hepatitis C / genetics*
  • Hepatitis C / immunology*
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Interleukins / immunology
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Prospective Studies

Substances

  • interferon-lambda, human
  • Interleukins
  • Interferons