Immune-inflammatory and genetic factors in the development of alcoholic liver fibrosis

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To evaluate the role of immune-inflammatory and genetic factors in the development of liver fibrosis in patients with alcohol liver disease (ALD).

Material and methods

Forty-six patients with ALD (35 males, mean age 50.2±11.5 years) were enrolled in our study and were distributed into two groups depending on the stage of liver fibrosis, that was determined by transient elastometry (F0+1, n=10; F3+4, n=36). We measured serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α , VEGF-A, sICAM-1, ET-1 levels and gene polymorphism of TNF-α (rs1800629 ), IL- 6 (rs1800795 ), VEGF-A (rs699947 ), ICAM1 (rs281437 ), ET-1 (rs1800541 ), IL-8 (rs4073 ).


Serum IL-6, IL-8, TNF-α , VEGF-A, sICAM-1 levels in patients with ALD were higher than the reference values. Serum IL-6, IL-8, sICAM-1 and ET-1 levels depended on the degree of alcoholic liver fibrosis. Degree of liver fibrosis sig- nificantly correlated with IL-6 (r = 0.60), IL-8 (r = 0.77), sICAM-1 (r = 0.58) and ET-1 (r = 0.56). There were no significant differences in the TNF-α and VEGF-A levels between the two groups. Different alleles and genotypes of the studied genes occurred with similar frequency in the two groups. In both groups, VEGF-A level in patients with genotypes CA of the rs699947 C2578A gene was higher than in patients with genotype AA (p = 0.04 and p = 0.01). In advanced fibrosis, genotype TT of the rs281437 -451CT gene was associated with a higher sICAM-1 compared with genotype CC (p=0.05)


Patients with ALD presented with increased levels of proinflammatory cytokines (IL-6, IL-8) and molecules of endothelial dysfunction (EТ1, sICAM-1). Genotype CA of the rs699947 gene was associated with a higher serum VEGF-A level in patients with ALD, while sICAM-1 level was in - creased in patients with genotype TT of the rs281437 gene and severe liver fibrosis.

Key words

Liver fibrosis, alcoholic liver disease, cytokines, endothelial dysfunction, genetic polymorphism.