Inflammation and insulin resistance in the progression of early forms of non-alcoholic fatty liver disease

The goal was to determine the role of inflammation and insulin resistance in early forms of nonalcoholic fatty liver diseases (NAFLD) - hepatic steatosis (HS) and steatohepatitis of mild activity (SHMA). Materials and methods. 220 patients with NAFLD were examined: 70 (31.8%) with HS and 150 (68.2%) with SHMA. The diagnosis was made according to the Russian Gastroenterological Association and Scientific Society of Gastroenterologists of Russia recommendations. Blood levels of tumor necrotic factor alpha (TNF-α) (ELISA, Human TNFα Platinum ELISA, eBioscience, Austria), interleukin-6 (IL-6) (Interleukin-6 - IFA-Best, Russia), insulin (Insulin TEST System, USA), cytokeratin-18 (CK-18) (ELISA, TPS ELISA, Biotech, Sweden), HOMA-IR (glycemia x insulin/22.5) and NAFLD fibrosis score (NAFLD FS) were evaluated. The control group consisted of 43 healthy donors. Statistical data processing was performed using «Statgraph 2.1» with estimation of Mann-Whitney and Spearman methods. Results. The frequency of the increase of TNF-α in blood was 74.3% in HS, 84.0% in SHMA, 47.1% and 50.7% for IL-6, and 40.0% and 54.0% for HOMA-IR, respectively. The content of TNF-α in HS was 5.9±1.7 pg/ml, in SHMA - 6.4±2.0 pg/ml, in healthy individuals - 4.3±1.3 pg/ml (p<0.05); as well as the content of IL-6 in HS - 5.4±2.8 pg/ml, in SHMA - 11.2±7.1 pg/ml, in healthy individuals - 1.0±0.4 pg/ml (p<0.05). The level of HOMA-IR in HS was 4.7±2.6, in SHMA - 10.5±2.3, in healthy individuals - 1.1±0.6 (p<0.05). TNF-α was correlated with HOMA-IR (r=0.64, p=0.003), CK-18 (r=0.66, p=0.008), leukocytes (r=0.59, p=0.002), NAFLD FS (r=0.34, p=0.04), HDL (r=-0.42, p=0.04) in HS; with HOMA-IR (r=0.67, p=0.004), NAFLD FS (r=0.60, p=0.016) and ALAT (r=0.23, p=0.04) in SHMA. IL-6 was correlated with ESR (r=0.51, p=0.04), leukocytes (r=0.49, p=0.04), triglycerides (r=0.73, p=0.016) and HDL (r=-0.52, p=0.04) in HS; with NAFLD FS (r=0.70, p=0.02) in SHMA. Conclusion. In the early forms of NAFLD - hepatic steatosis and steatohepatitis of mild activity - an increased levels of pro-inflammatory cytokines - TNF-α, IL-6 and HOMA-IR were observed. Both cytokines correlated with conventional markers of inflammation, dyslipidemia, fibrosis and TNF-α - with HOMA-IR and hepatocyte damage markers. These facts confirmed the role of low-level inflammation and insulin resistance in the progression of early forms of NAFLD.

стеатоз печени, стеатогепатит слабой активности, ТНФ-α, ИЛ-6, инсулинорезистентность, hepatic steatosis, steatohepatitis, TNF-α, IL-6, insulin resistance