Study of the role of biomarkers in determining the course of non-alcoholic fatty liver disease in children with obesity

• Lebedeva A.M.
• Elena V. Pavlovskaya
• Madlena E. Bagaeva
• Natalia N. Taran
• Andrey I. Zubovich
• Irina A. Matinyan
• Ekaterina A. Kiselnikova
• Tatyana V. Strokova

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, especially among children. Studying the role of biomarkers in determining the course of NAFLD in obese children will make it possible to identify the disease at an early stage, assess the risks of progression and select individual approaches to therapy.

The purpose of the research was to study the diagnostic role of noninvasive biomarkers in determining the severity of liver steatosis and fibrosis in obese children.

Material and methods. 78 children from 11 to 17 years of age with exogenous constitutional obesity were examined. The children were divided into two groups: group 1 (n=59) – children with obesity and non-alcoholic fatty liver disease (NAFLD), group 2 (n=19) – children without NAFLD; in group 1, subgroups of children with simple liver steatosis (n=45) and non-alcoholic steatohepatitis (NASH) were identified (n=14). The study of lipid metabolism (total cholesterol, HDL, LDL, triglycerides), carbohydrate metabolism (glucose, insulin, HOMA-IR), blood serum level of fibroblast growth factor-21 (FGF-21), cytokeratin-18 (СK18), apoptosis factor associated with the FAS ligand (FASL), and visfatin has been conducted. All patients underwent ultrasound examination of the abdominal organs and liver elastography to determine the degree of liver fibrosis on the METAVIR scale and the degree of steatosis using a controlled attenuation parameter (CAP).

Results. The level of the biomarkers CK-18 and FASL were significantly higher in children from Group 1 compared to those without NAFLD (1.26 [0.44; 1.57] vs 0.47 [0.43; 0.59] ng/mL, p=0.008 and 36.33 [25.57; 45.94] vs 22.55 [20.27; 26.41] pg/mL, respectively). Moreover, these levels increased with the degree of obesity. In patients with NASH, FASL levels showed a positive correlation with the degree of obesity (r=0.40), CK-18 with the stage of liver fibrosis (r=0.50), and visfatin with transaminase activity (r=0.65), fibrosis (r =1.0), and hepatic steatosis degree (r=0.60). FGF-21 demonstrated only weak correlations with the other studied biomarkers. The HIS and APRI indices were significantly higher in patients with NASH (46.46 [40.75; 53] vs 42.11 [36.88; 47.09], p=0.0006 and 0.25 [0.18; 0.36] vs 0.18 [0.15; 0.21], p=0.04 in patients with hepatic steatosis; and vs 40.02 [36.4; 44.85] and 0.16 [0.12; 0.22] in patients from Group 2, respectively). All patients had PNFI>9, indicating the presence of significant fibrotic changes. Correlation analysis showed that HIS and APRI indices were strongly associated with the degree of steatosis, alanine aminotransferase activity, and right liver lobe size.

Conclusion. The use of biomarkers makes it possible to complement ultrasound diagnostics of NAFLD, providing more complete information about the severity of the disease without invasive procedures. The development and application of noninvasive methods for the diagnosis and prediction of NAFLD will in some cases avoid liver biopsy.

Keywords: children; non-alcoholic fatty liver disease; steatohepatitis; obesity; diagnosis; FGF-21; cytokeratin-18; FASL; visfatin

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