Inflammatory cytokines, soluble interleukin-6 receptors, and fragmented cytokeratin-18 as indicators of non-alcoholic steatohepatitis

Aim. To evaluate inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, 8, 6, soluble IL-6 receptors (sIL-6R) and fragmented cytokeratin-18 (FCK-18) as indicators of non-alcoholic steatohepatitis (NASH). Materials and methods. 173 NASH patients aged 47.0±10.8 years were examined: 118 (68.2%) – men, 55 (31.8%) – women. The following markers were determined: TNF-α (Human TNFα Platinum ELISA, eBioscience, Austria), IL-1β, 8, 6 (Vector-Best, Russia), sIL-6R (Human sIL-6R ELISA, eBioscience, Austria), FCK-18 (TPS ELISA, Biotech, Sweden), insulin (Insulin TEST System, USA), HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) and NAFLD fibrosis score (NFS) were calculated. Results. The highest level in NASH patients compared with healthy individuals was observed for IL-6 – 8.4±1.6 pg/ml versus 2.8±0.9 pg/ml (p=0.001), FCK-18 – 295.3±56.3 U/l versus 110.5±30.2 U/l (p=0.0001), then IL-8 – 17.3±6.7 pg/ml vs 7.6±1.9 pg/ml (p=0.003), TNF-α – 6.3±0.4 pg/ml versus 4.1±0.8 pg/ml (p=0.0001), sIL-6R – 151.5±21.2 ng/ml vs 95.9±12.5 ng/ml (p0.05); IL-1β did not change – 5.3±1.4 pg/ml versus 4.7±1.5 pg/ml (p=0.3) respectively. FCK-18 showed the highest correlations with TNF-α (r=0.73), HOMA-IR (r=0.73), alanine aminotransferase (r=0.71), erythrocyte sedimentation rate (r=0.23), IL-6 (r=0.22); p0.05. TNF-α correlated with FCK-18 (r=0.73), cholesterol (r=0.61), albumin (r=-0.42), fibrinogen (r=0.21), leukocyte count (r=0.21); p0.05. IL-8 correlated with triglycerides (r=0.79) and HDL (r=-0.77), IL-6 – with NFS (r=0.63) and FCK-18 (r=0.22), rIL-6R – with aspartate aminotransferase (r=0.62); p0.05. Conclusion. TNF-α, IL-8, 6, sIL-6R and FCK-18 should be used as non-invasive biomarkers of NASH.