Cytokines in alcoholic liver disease

Material and methods

Ninety patients with ALD [67 male, median age 50 (IQR 43-59) years] were included in our study. They were divided into 4 groups depending on the stage of liver fibrosis: 1) F0, n=25; 2) F1-2, n=20; 3) F3 + F4 (class А according to Child-Pugh score), n=27; 4) F4 (class В, С according to Child-Pugh score), n=18. The stage of liver fibrosis was determined by transient elastometry (Fibro Scan®). Exclusion criteria were chronic non-alcoholic liver disease and acute alcoholic hepatitis. We analyzed serum concentrations of interleukin (IL)-6, IL-8, IL12p70, IL12p40, transforming growth factor beta-1 (TGF-β1). The control group consisted of 15 healthy volunteers (10 male, 48 ± 8,2 years).

Results

In patients with ALD serum concentration of IL-6, IL-8, TGF-β1 were higher than in the control group (p <0.005). The levels of IL-6 and IL-8 depended on the degree of alcoholic liver fibrosis. In the group 2, they were higher than in the groups 1 (p<0,05) and 3 (p<0,05), while in the group 4 they were higher than in the group 1 (p <0.005). Liver stiffness correlated (p<0,05) with serum concentration of IL-6 (r=0,354), IL-8 (r=0,580) and TGF-β1 (r=-0,345). Also we found a positive correlation of serum IL-6 and IL-8 with serum total and direct bilirubin and negative correlation with synthetic liver function (prothrombin index, cholinesterase). There were significant positive correlation between the active subunit of IL-12 (IL12p40) and platelet counts and significant negative correlation between TGF-β1 and platelet counts.

Conclusion

In patients with ALD, there were increased levels of IL-6, IL-8 and TGF-β1. Progression of alcoholic liver fibrosis was associated with changes in interleukins levels. Liver stiffness correlated with levels of proinflammatory and profibrogenic cytokines. IL-12 had no impact on development ALD and alcoholic fibrosis.

Key words

Cytokines, alcoholic cirrhosis, liver fibrosis, liver stiffness.