Genetic polymorphisms of interleukin-1-beta in association with sustained response to anti-viral treatment in chronic hepatitis B in Chinese.
BACKGROUND
Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection.


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


METHODS
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).


CONCLUSIONS
High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.
Chan
H L-Y
HL
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong. hlychan@cuhk.edu.hk
Tse
A M-L
AM
Zhang
M-D
MD
Wong
V W-S
VW
Chim
A M-L
AM
Hui
A Y
AY
Sung
J J-Y
JJ
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000235:genetics*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007375:Interleukin-1; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a