Pathogenetic role of inflammation and insulin resistance in non-alcoholic fatty liver disease in obese children

Abstract

The hypothesis of primacy between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) remains debatable, which requires additional research. Aim. To examine the differences between cytokine profile and IR markers in children with NAFLD depending on liver damage degree compared to children with normal weight and obesity without NAFLD and to study their association with anthropometric and instrumental parameters. Materials and methods. 170 patients aged 6–17 years (mean 12.15 ± 2.51 years) were included. Hepatic steatosis was determined by transient elastography. Patients were divided into 4 groups according to the presence of hepatic steatosis, non-alcoholic steatohepatitis (NASH) and obesity: group 1 – 37 obese patients with NASH; group 2 – 53 obese patients with simple steatosis; group 3 – 65 obese patients without NAFLD; group 4 (control) – 15 patients with normal weight without NAFLD. Anthropometric parameters, carbohydrate metabolism with the HOMA-IR calculation, and cytokine profile were examined. Results. An increase in serum IL-6 and TNFα levels in NAFLD children compared to the control group (P ˂ 0.05), a decrease in IL-10 level in NAFLD children (P ˂ 0.05), and an increase in TNFα/IL-10 ratio (P ˂ 0.05) in NASH children compared to obese children without steatosis were demonstrated. In NAFLD children, a progressive increase in HOMA-IR was found compared to the control group and obese children without steatosis (P ˂ 0.05). The serum IL-6, TNFα levels, TNFα/IL-10 ratio, and HOMA-IR were positively correlated with obesity degree, adipose tissue distribution parameters, hepatic steatosis degree, CAP, while IL-10 level was negatively correlated with the hepatic steatosis degree. Conclusions. In obese NAFLD children, a significant increase in HOMA-IR, IL-6, TNFα is correlated with excessive fat accumulation, adipose tissue distribution parameters, hepatic steatosis degree, and CAP that may be useful for early diagnosis of NAFLD in children. A significant increase in the TNFα/IL-10 ratio in NASH children allows to consider this indicator as a probable marker for diagnosis of different NAFLD forms in pediatric clinical practice.

Keywords

• fatty liver
• insulin resistance
• inflammation
• obesity
• children