Lebedeva A M, Pavlovskaya E V, Bagaeva M E, Taran N N, Zubovich A I, Matinyan I A, Kiselnikova E A, Strokova T V
Federal Research Centre of Nutrition, Biotechnology and Food Safety, 109240, Moscow, Russian Federation.
Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, 123995, Moscow, Russian Federation.
Vopr Pitan. 2025;94(2):85-96. doi: 10.33029/0042-8833-2025-94-2-85-96. Epub 2025 Mar 17.
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. of the research was to study the diagnostic role of noninvasive biomarkers in determining the severity of liver steatosis and fibrosis in obese children. . 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). . 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. . 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.
非酒精性脂肪性肝病(NAFLD)是世界上最常见的慢性肝病之一,在儿童中尤为常见。研究生物标志物在确定肥胖儿童NAFLD病程中的作用,将有助于在疾病早期进行识别,评估疾病进展风险,并选择个体化的治疗方法。本研究的目的是探讨非侵入性生物标志物在确定肥胖儿童肝脂肪变性和纤维化严重程度方面的诊断作用。对78名11至17岁的外源性体质性肥胖儿童进行了检查。这些儿童被分为两组:第1组(n = 59)——患有肥胖症和非酒精性脂肪性肝病(NAFLD)的儿童,第2组(n = 19)——无NAFLD的儿童;在第1组中,又确定了单纯性肝脂肪变性儿童亚组(n = 45)和非酒精性脂肪性肝炎(NASH)儿童亚组(n = 14)。对脂质代谢(总胆固醇、高密度脂蛋白、低密度脂蛋白、甘油三酯)、碳水化合物代谢(葡萄糖、胰岛素、HOMA-IR)、成纤维细胞生长因子-21(FGF-21)、细胞角蛋白-18(СK18)、与FAS配体相关的凋亡因子(FASL)和内脂素的血清水平进行了研究。所有患者均接受了腹部器官超声检查和肝脏弹性成像检查,以根据METAVIR量表确定肝纤维化程度,并使用受控衰减参数(CAP)确定脂肪变性程度。与无NAFLD的儿童相比,第1组儿童的生物标志物CK-18和FASL水平显著更高(分别为1.26 [0.44;1.57] vs 0.47 [0.43;0.59] ng/mL,p = 0.008和36.33 [25.57;45.94] vs 22.55 [20.27;26.41] pg/mL)。此外,这些水平随着肥胖程度的增加而升高。在NASH患者中,FASL水平与肥胖程度呈正相关(r = 0.40),CK-18与肝纤维化阶段呈正相关(r = 0.50),内脂素与转氨酶活性呈正相关(r = 0.65)、与纤维化呈正相关(r = 1.0)以及与肝脂肪变性程度呈正相关(r = 0.60)。FGF-21仅与其他研究的生物标志物显示出微弱的相关性。NASH患者的HIS和APRI指数显著更高(分别为46.46 [40.75;53] vs 42.11 [36.88;47.09],p = 0.0006和0.25 [0.18;0.36] vs 0.18 [0.15;0.21],肝脂肪变性患者中p = 0.04;与第2组患者相比,分别为40.02 [36.4;44.85]和0.16 [0.12;0.22])。所有患者的PNFI>9,表明存在明显的纤维化改变。相关性分析表明,HIS和APRI指数与脂肪变性程度、丙氨酸转氨酶活性和右肝叶大小密切相关。使用生物标志物可以补充NAFLD的超声诊断,在不进行侵入性检查的情况下提供有关疾病严重程度的更完整信息。NAFLD诊断和预测的非侵入性方法的开发和应用在某些情况下将避免肝活检。