The role of systemic inflammation in the pathogenesis and progression of nonalcoholic fatty liver disease in children
Background. Progression of nonalcoholic fatty liver disease occurs in genetically predisposed children due to the development of systemic and local inflammatory response in the liver parenchyma closely related to the formation of insulin resistance. The accumulated data indicates that patients with nonalcoholic fatty liver disease are characterized by a high level of serum inflammatory markers. The aim of the present study was to establish the relationship between blood lipids, insulin resistance, anthropometric data, indicators of systemic inflammation and the degree of liver steatosis in children with nonalcoholic fatty liver disease; to assess the role of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 in the progression of nonalcoholic fatty liver disease in children. Materials and methods. We examined 34 children aged 6–17 years. Determination of the presence and degree of hepatic steatosis was made using FibroScan® 502-touch with evaluation of the controlled attenuation parameter (CAP). Patients were divided into 3 groups according to CAP level: a control group (S0) consisted of 21 patients without hepatic steatosis (61.8 %), group S1 — 4 persons with grade 1 steatosis (11.8 %), group S2 — 4 patients with grade 2 steatosis (11.8 %), group S3 — 5 individuals with grade 3 steatosis (14.8 %). All patients underwent anthropometric measurements, blood tests with determination of erythrocyte sedimentation rate, level of leukocytes and leukocyte formula. We studied levels of the IL-6, IL-10, TNF-α, insulin in the blood serum, also serum samples were tested for total cholesterol, triglycerides (TG), high density lipoprotein (HDL) cholesterol with calculation of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) levels, atherogenic index. Results. Obesity and overweight were observed in 100 % of children in S1. S2, S3 groups, and in 47.6 % of patients without steatosis (S0 group) (p < 0.05). We revealed that S3 group was characterized by higher average levels of white blood cells (7.13 ± 0.51 g/l) and erythrocyte sedimentation rate (15.50 ± 4.04 mm/h) compared with S0 group (5.34 ± 1.17 g/l, 10.19 ± 7.74 mm/h, respectively; p < 0.05).We found that insulin level increased with growth of steatosis grade: in group S0 — by 1.3 times, group S1 — by 2.4 times, group S2 — by 2.8 times and in S3 group — by 6.3 times compared to the controls. Also, we found a presence of significant differences between the content of HDL cholesterol in groups S3 and S0. The level of TG (r = 1.0;
p < 0.05) and VLDL (r = 0.8; p = 0.04) positively correlated with the level of insulin, and showed a negative correlation with HDL level (r = –0.7; p < 0.05). Maximum levels of TNF-α were observed in group S3 (1.8 ± 0.8 pg/ml), which differed significantly from S0 group and other groups with steatosis. The level of IL-6 increased progressively with growth of steatosis grade: S0 — 1.2 ± 0.2 pg/ml, S1 — 1.55 ± 0.30 pg/ml, S2 — 4.8 ± 0.5 pg/ml, S3 — 6.1 ± 0.5 pg/ml. Level of anti-inflammatory cytokine IL-10 changed ambiguous: the minimum level of this index was in S1 group, that was significantly lower comparing to S0 group. The concentration of IL-10 reached maximum value in S2 group (9.5 ± 1.1 pg/ml)
and critically decreased in patients from S3 group. Conclusions. Nonalcoholic fatty liver disease in children manifested by imbalance of pro- and anti-inflammatory cytokines with increase of IL-6, TNF-α and decrease in IL-10 level was associated with the grade of hepatic steatosis on the background of dyslipidemia and insulin resistance.
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