Genetic polymorphisms of interleukin-1-beta in association with sustained response to anti-viral treatment in chronic hepatitis B in Chinese

Aliment Pharmacol Ther. 2006 Jun 15;23(12):1703-11. doi: 10.1111/j.1365-2036.2006.02948.x.

Abstract

Background: Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection.

Aim: To investigate the impact of interleukin-1beta gene polymorphism on the response to anti-viral treatment.

Method: Hepatitis B e antigen-positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha-2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post-treatment. Polymorphisms at interleukin-1beta-511, -31 and -3954 and interleukin-1 receptor antagonist (RN) were studied.

Results: Eighty-eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin-1beta-511 and -31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre-treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin-1beta-511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin-1beta-511 (83%) than those without (70%) (P = 0.058).

Conclusion: High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Asian People / ethnology
  • Asian People / genetics
  • Female
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interleukin-1 / genetics*
  • Lamivudine / therapeutic use*
  • Male
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Genetic / genetics*
  • Recombinant Proteins
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukin-1
  • Recombinant Proteins
  • Lamivudine
  • Polyethylene Glycols
  • peginterferon alfa-2a