Association of cytokine gene polymorphisms and liver fibrosis in chronic hepatitis B.

J Gastroenterol Hepatol 2008 May 21;23(5):783-9. Epub 2007 Jul 21.

Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.

Background And Aim: As liver fibrosis is the result of persistent necroinflammation in the liver, pro-inflammatory cytokines secreted in response to cell injury have a central role in the pathogenesis of liver fibrosis. We aimed to investigate the association of cytokine gene polymorphism and liver fibrosis among Chinese patients with chronic hepatitis B.

Methods: Polymorphisms at interleukin-10 (IL-10-627, -1117), interleukin-1-beta (IL-1beta-511, -31, -3964), interleukin-1 receptor antagonist (IL-1RN), and tumor necrosis factor-alpha (TNF-alpha-308, -238) among Chinese chronic hepatitis B patients were determined. Severe liver fibrosis was defined as Ishak fibrosis score = 4 (of 6).

Results: Fifty-nine of 273 (22%) patients had severe fibrosis. The distribution of genotypes for IL-10-627 was CC (11%), CA (41%), and AA (48%). The CC genotype at IL-10-627 was protective against severe fibrosis (odds ratio (OR) 0.11; 95% CI 0.014-0.82; P = 0.032). After adjusted for baseline variables, the adjusted OR of CC genotypes at IL-10-627 for severe fibrosis was 0.063 (95% CI 0.06-0.64; P = 0.063). Other gene polymorphisms at IL-1beta, IL-1RN, TNF-alpha, and IL-10 had no significant association with severe fibrosis. Weak linkage disequilibrium was observed between IL-10-627 and IL-10-1117 with linkage disequilibrium coefficient of 0.12 (P < 0.001). The distribution of haplotypes of IL-10-1117 and IL-10-627 was A-A (69%), A-C (26%), and G-C (5%). High and intermediate IL-10 production (A-C and G-C) haplotypes were protective against severe fibrosis (OR 0.62; 95% CI 0.39-0.99; P = 0.046).

Conclusions: High production genotype and haplotypes of IL-10 were associated with less severe liver fibrosis in chronic hepatitis B in Chinese.

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http://doi.wiley.com/10.1111/j.1440-1746.2007.05110.x
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http://dx.doi.org/10.1111/j.1440-1746.2007.05110.xDOI Listing
May 2008
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Takamatsu M et al.
Am. J. Gastroenterol. 2000

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