Article

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

Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Alimentary Pharmacology & Therapeutics (Impact Factor: 5.48). 07/2006; 23(12):1703-11. DOI: 10.1111/j.1365-2036.2006.02948.x
Source: PubMed

ABSTRACT Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection.
To investigate the impact of interleukin-1beta gene polymorphism on the response to anti-viral treatment.
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.
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).
High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.

Full-text

Available from: Vincent Wai-Sun Wong, Dec 30, 2014
0 Followers
 · 
57 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Certain host genetic polymorphisms in interferon (IFN) signaling pathway genes are reported to be associated with response to IFNα therapy. We studied 10 single nucleotide polymorphisms (SNPs) in IFN signaling pathway genes to examine their associations with response to IFN treatment in chronic hepatitis B (CHB) patients. Two hundred and forty-six IFNα treatment-naïve CHB patients were enrolled for the present study; all received treatment with IFNα alone for 6 months, and the efficacy of the therapy was examined. Ten SNPs in 8 IFN signaling pathway genes were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. There were no significant differences in allele frequencies and genotype distributions of the 10 SNPs between the response and non-response groups that underwent IFNα therapy. However, the frequency of a G-T-G-A 2′,5′-oligoadenylate synthetase (OAS) haplotype was significantly higher in the non-response group than that in the response group (16.1% vs. 8.7%, p=0.015). Our study suggested that patients with a G-T-G-A OAS haplotype were less responsive to IFNα treatment.
    Antiviral research 01/2009; 83(3):252-256. DOI:10.1016/j.antiviral.2009.06.003 · 3.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although chronic hepatitis B (CHB) is a global health threat, it is now a preventable and treatable disease. Seven agents have been approved for the treatment of CHB. Although many patients prefer potent long-term nucleos(t)ide analogues (NAs) as the first-line therapy because they are convenient to use and well-tolerated, a finite duration of pegylated interferon (PEG-IFN) is still an attractive strategy because it provides higher rates of off-therapy host immune control over hepatitis B virus (HBV) compared with NAs. In addition, the rates of HBeAg/HBsAg loss or seroconversion increase over time in patients who respond to PEG-IFN therapy. Nevertheless, these benefits are limited to 30% of all patients, and significant adverse effects are still a concern. Therefore, patients who can benefit most from PEG-IFN therapy should be more carefully selected according to baseline host and viral predictors, such as age, ALT level, viral load, HBV genotype and HBV mutants. In addition, on-treatment predictors including HBV DNA, HBeAg and HBsAg kinetics, can help decide who should continue or discontinue PEG-IFN and shift to NA. Understanding these factors can help determine personalized PEG-IFN therapy for CHB patients. In the near future, the treatment paradigm of CHB should be tailored on the basis of viral (HBV DNA level, HBV genotype and HBV mutants) and host (age, gender, ALT level and host genetic polymorphisms) factors, disease status (stage of fibrosis and comorbidities) and the selection of antiviral agents (immunomodulatory effect, antiviral potency, adverse effects and rate of drug resistance).
    Liver international: official journal of the International Association for the Study of the Liver 02/2014; 34 Suppl 1:112-9. DOI:10.1111/liv.12400 · 4.41 Impact Factor
  • Source
    European Neuropsychopharmacology 08/2010; 20. DOI:10.1016/S0924-977X(10)70463-6 · 5.40 Impact Factor