| Description: |
The aim of the study is to evaluate the diagnostic information value of direct serological biomarkers — hyaluronic acid (HA), collagen types I and III (COL1, COL3), growth differentiation factor-15 (GDF-15), monocyte chemotactic factor-1 (MCP-1) and extracellular matrix protein 1 (ECM1) — for noninvasive stage identification hepatic fibrosis (HF) in children.Material and methods. The study included 60 patients (average age 10.2 ± 4.7 years) with chronic liver diseases of various etiologies, including autoimmune hepatitis (16), primary sclerosing cholangitis (11), glycogen disease (10), Wilson’s disease (6), and unspecified HF (17). All children underwent ultrasound examination of the abdominal organs with two-dimensional shear wave elastography (2D-SWE) and quantitative determination of the above markers in the blood serum. The concentrations of HA in the blood serum of patients were determined by enzyme-linked immunosorbent assay (ELISA); COL1, COL3, ECM1, GDF-15 and MCP-1 were determined by sandwich ELISA.Results. The concentrations of HA and GDF-15 in blood serum increased statistically significantly with the progression of HF (p < 0.001; p = 0.001, respectively). To determine the threshold values of HA depending on the stages of HF, high sensitivity (90%) and specificity (up to 100%) were obtained, and the best values of the area under the ROC-curve were used to distinguish the late stages of fibrosis (AUC up to 0.965). The concentrations of GDF-15 in serum are characterized by maximum sensitivity when determining cut-off values to determine the stage of severe fibrosis and its initial manifestations, the specificity for close stages was lower (up to 70%). The concentrations of COL1, COL3, MCP-1, and ECM1 did not show significant differences between the HF stages (p = 0.108; p = 0.455; p = 0.158; p = 0.058, respectively). Direct correlations were found between serum levels of COL1 and COL3 (p = 0.341, p = 0.008), HA and GDF15 (p = 0.592, p < 0.001), MCP-1 and COL3 (p = 0.443, p < 0.001), as well as ... |
| Relation: |
https://www.pedpharma.ru/jour/article/view/2728/1758; Кулебина Е.А., Сурков А.Н. Прогресс неинвазивной диагностики фиброза печени: обзор современных лабораторных методик // Медицинский совет. — 2020. — № 11. — С. 224-232. — doi: https://doi.org/10.21518/2079-701X-2020-11-224-232; Кулебина Е.А., Сурков А.Н., Усольцева О.В. Неинвазивная диагностика фиброза печени: возможности инструментальных методик на современном этапе // РМЖ. Медицинское обозрение. — 2020. — Т. 4. — № 5. — С. 297–301. — doi: https://doi.org/10.32364/2587-6821-2020-4-5-297-301; Rojano-Alfonso C, López-Vicario C, Romero-Grimaldo B, et al. Hyaluronic Acid in Liver Fibrosis: Role in Inflammation, Tissue Remodeling, and Disease Progression. Int J Mol Sci. 2025;26(20):10139. doi: https://doi.org/10.3390/ijms262010139; Кулебина Е.А., Сурков А.Н., Алябьева Н.М. и др. Изменения сывороточных концентраций прямых биомаркеров фиброзирования при хронических болезнях печени у детей // Педиатрия. Журнал им. Г.Н. Сперанского. — 2021. — Т. 100. — № 2. — С. 112–118. — doi: https://doi.org/10.24110/0031-403X-2021-100-2-112-118; Graf F, Horn P, Ho AD, et al. The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells. FASEB J. 2021;35(7):e21692. doi: https://doi.org/10.1096/fj.202002558RR; Selvaraj V, Sekaran S, Dhanasekaran A, Warrier S. Type 1 collagen: Synthesis, structure and key functions in bone mineralization. Differentiation. 2024;136:100757. doi: https://doi.org/10.1016/j.diff.2024.100757; Kuivaniemi H, Tromp G. Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases. Gene. 2019;707:151–171. doi: https://doi.org/10.1016/j.gene.2019.05.003; Singh D, Rai V, Agrawal DK. Regulation of Collagen I and Collagen III in Tissue Injury and Regeneration. Cardiol Cardiovasc Med. 2023;7(1):5–16. doi: https://doi.org/10.26502/fccm.92920302; Desmedt S, Desmedt V, De Vos L, et al. Growth differentiation factor 15: A novel biomarker with high clinical potential. Crit Rev Clin Lab Sci. 2019;56(5):333–350. doi: https://doi.org/10.1080/10408363.2019.1615034; Huang J, Ding X, Dong Y, Zhu H. Growth Differentiation Factor-15 Orchestrates Inflammation-Related Diseases via Macrophage Polarization. Discov Med. 2024;36(181):248–255. doi: https://doi.org/10.24976/Discov.Med.202436181.23; Nyárády BB, Kiss LZ, Bagyura Z, et al. Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease. Biomed Pharmacother. 2024;174:116475. doi: https://doi.org/10.1016/j.biopha.2024.116475; Delrue C, Speeckaert R, Delanghe JR, Speeckaert MM. Growth differentiation factor 15 (GDF-15) in kidney diseases. Adv Clin Chem. 2023;114:1–46. doi: https://doi.org/10.1016/bs.acc.2023.02.003; Siddiqui JA, Pothuraju R, Khan P, et al. Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia. Cytokine Growth Factor Rev. 2022;64:71–83. doi: https://doi.org/10.1016/j.cytogfr.2021.11.002; Lee ES, Kim SH, Kim HJ, et al. Growth Differentiation Factor 15 Predicts Chronic Liver Disease Severity. Gut Liver. 2017;11(2):276–282. doi: https://doi.org/10.5009/gnl16049; Arinaga-Hino T, Ide T, Akiba J, et al. Growth differentiation factor 15 as a novel diagnostic and therapeutic marker for autoimmune hepatitis. Sci Rep. 2022;12(1):8759. doi: https://doi.org/10.1038/s41598-022-12762-9; Li Z, Liu Y, Li X, et al. Association between Circulating Growth Differentiation Factor 15 and Cirrhotic Primary Biliary Cholangitis. Biomed Res Int. 2020;2020:5162541. doi: https://doi.org/10.1155/2020/5162541; Abou Zaghla HMA, El Sebai AA, Ahmed OA, et al. Growth differentiation factor 15: an emerging diagnostic biomarker of liver fibrosis in chronic hepatitis C patients. Egypt Liver J. 2021;11(1):6. doi: https://doi.org/10.1186/s43066-021-00075-x; Sawant H, Borthakur A. Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis. Int J Mol Sci. 2025;26(12):5713. doi: https://doi.org/10.3390/ijms26125713; Xi S, Zheng X, Li X, et al. Activated Hepatic Stellate Cells Induce Infiltration and Formation of CD163+ Macrophages via CCL2/CCR2 Pathway. Front Med (Lausanne). 2021;8:627927. doi: https://doi.org/10.3389/fmed.2021.627927; Guo S, Zhang Q, Guo Y, et al. The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases. Front Immunol. 2025;15:1497026. doi: https://doi.org/10.3389/fimmu.2024.1497026; Tsai PH, Liou LB. Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1. Int J Mol Sci. 2024;25(21):11374. doi: https://doi.org/10.3390/ijms252111374; Singh S, Anshita D, Ravichandiran V. MCP-1: Function, regulation, and involvement in disease. Int Immunopharmacol. 2021;101(Pt B):107598. doi: https://doi.org/10.1016/j.intimp.2021.107598; Kobayashi K, Yoshioka T, Miyauchi J, et al. Role of monocyte chemoattractant protein-1 in liver fibrosis with transient myeloproliferative disorder in down syndrome. Hepatol Commun. 2018;2(3):230–236. doi: https://doi.org/10.1002/hep4.1150; Bauer A, Rawa T. Circulating Monocyte Chemoattractant Protein-1 (MCP-1) in Patients with Primary Biliary Cholangitis. Int J Mol Sci. 2024;25(2):1333. doi: https://doi.org/10.3390/ijms25021333; Wang J, Huang Q, Ning H, et al. Extracellular matrix protein 1 in cancer: multifaceted roles in tumor progression, prognosis, and therapeutic targeting. Arch Pharm Res. 2025;48(9-10):843–857. doi: https://doi.org/10.1007/s12272-025-01572-y; Sun C, Fan W, Basha S, et al. Extracellular matrix protein 1 binds to connective tissue growth factor against liver fibrosis and ductular reaction. Hepatol Commun. 2024;8(11):e0564. doi: https://doi.org/10.1097/HC9.0000000000000564; Link F, Li Y, Zhao J, et al. ECM1 attenuates hepatic fibrosis by interfering with mediators of latent TGF-β1 activation. Gut. 2025;74(3):424–439. doi: https://doi.org/10.1136/gutjnl-2024-333213; Fan W, Liu T, Chen W, et al. ECM1 Prevents Activation of Transforming Growth Factor β, Hepatic Stellate Cells, and Fibrogenesis in Mice. Gastroenterology. 2019;157(5):1352–1367. e13. doi: https://doi.org/10.1053/j.gastro.2019.07.036; Mosca A, Braghini MR, Andolina G, et al. Levels of Growth Differentiation Factor 15 Correlated with Metabolic DysfunctionAssociated Steatotic Liver Disease in Children. Int J Mol Sci. 2025;26(13):6486. doi: https://doi.org/10.3390/ijms26136486; Hartley JL, Brown RM, Tybulewicz A, et al. Hyaluronic acid predicts hepatic fibrosis in children with hepatic disease. J Pediatr Gastroenterol Nutr. 2006;43(2):217–221. doi: https://doi.org/10.1097/01.mpg.0000228121.44606.9f; https://www.pedpharma.ru/jour/article/view/2728 |
| Rights: |
Authors who publish articles in this journal agree to the following:Authors retain the copyright for the work and grant the journal the right to publish the work for the first time, and license it in terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). It allows others to share the work with the obligatory preservation of references to the authors of the original and the original manuscript in the journal.Authors have the right to post their work on the Internet (for example, in college database or on personal website) before and during the reviewing process by this journal as it may lead to constructive discussion and more references to this work (see The Effect of Open Access).Copyright assignment clause: the author (or designated person) of the article have to copy the form of the Copyright Agreement, fill it out, scan it, and send it to the editorial office. ; Авторы, публикующие статьи в данном журнале, соглашаются на следующее:Авторы сохраняют за собой авторские права на работу и предоставляют журналу право первой публикации работы, одновременно лицензируя ее на условиях Creative Commons Attribution-NonCommercial 4.0 International (СС BY-NC 4.0), которая позволяет другим распространять данную работу с обязательным сохранением ссылок на авторов оригинальной работы и оригинальную публикацию в этом журнале.Авторы имеют право размещать их работу в сети Интернет (например в институтском хранилище или персональном сайте) до и во время процесса рассмотрения ее данным журналом, так как это может привести к продуктивному обсуждению и большему количеству ссылок на данную работу (См. The Effect of Open Access).Условия передачи авторских прав: Автору (уполномоченному лицу) статьи следует скопировать форму Авторского договора, заполнить ее, отсканировать и прислать в редакцию. |