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

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-1b511, -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-1b, 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-10-1 beta- with linkage disequilibrium coefficient of 0.12 ( P < 0.001). The distribution of hap-lotypes of IL-10- 1117 and IL-10-627 wasA-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.