Effects of polymorphisms in interferon λ 3 (interleukin 28B) on sustained virologic response to therapy in patients with chronic hepatitis D virus infection

Clin Gastroenterol Hepatol. 2014 Oct;12(10):1753-8. doi: 10.1016/j.cgh.2014.01.043. Epub 2014 Feb 26.

Abstract

Background & aims: We investigated the association between interferon λ 3 (IFNL3) genotype (also known as interleukin 28B) and response to IFNα therapy in patients with chronic hepatitis D virus (HDV) infection.

Methods: We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFNα and 13 patients (41%) were treated with standard IFNα, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6-164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses.

Results: After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 (P = .78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 (P = .30 for TT vs GT vs GG).

Conclusions: The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFNα.

Keywords: Chronic Delta Hepatitis; Immune Regulation; Interferon Lambda 3; SNP.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Genotype
  • Hepatitis D, Chronic / drug therapy*
  • Hepatitis Delta Virus / isolation & purification*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Models, Statistical
  • Polymorphism, Genetic*
  • RNA, Viral / blood
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Treatment Outcome
  • Viral Load*
  • Young Adult

Substances

  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Interferons