儿童青少年非酒精性脂肪性肝病及代谢相关脂肪性肝病诊断研究热点与趋势的可视化分析

Visualization analysis on research hotspots and trends in the diagnosis of nonalcoholic fatty liver disease in children and adolescents

摘要

目的 运用文献计量学方法分析2014—2024年间儿童青少年非酒精性脂肪性肝病(NAFLD)及代谢相关脂肪性肝病(MAFLD)诊断领域的研究热点与演进趋势,为未来研究方向提供参考依据。方法 检索2014年1月—2024年12月Web of Science(WOS)与中国知网(CNKI)数据库中的相关中英文文献,采用CiteSpace与VOSviewer软件,对年度发文量、核心研究机构、作者合作网络、关键词共现与聚类、突现词及共被引文献展开可视化分析。结果 共纳入英文文献1 341篇、中文文献319篇。中英文文献年发文量均呈增长趋势,其中英文文献增长更为显著。基于英文文献的网络显示,国际上形成以多学者为核心的多机构紧密合作网络;中文文献中则形成以小型团队为主的合作模式。排除检索词后,英文文献关键词中心性前三位为“obesity”、“metabolic syndrome”、“insulin resistance”;中文文献关键词中心性前三位为“肝纤维化”、“儿童肥胖”、“胰岛素抵抗”。中英文文献关键词聚类显示研究热点主要集中在儿童肥胖、代谢综合征、无创诊断技术及遗传机制,无创影像技术与复合生物标志物是近年来的研究前沿。结论 儿童青少年NAFLD/MAFLD诊断领域已形成以“肥胖-代谢紊乱-肝脏损伤”为核心的研究框架。当前研究趋势主要集中在无创诊断技术的改进以及对多系统代谢健康的整体评估。这为未来制定针对儿童的多维度诊断标准、整合多中心数据以及建立全程健康管理体系提供了循证依据。

Abstract

Objective To analyze research hotspots and evolving trends in the diagnosis of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in children and adolescents from 2014 to 2024 using bibliometric methods, so as to provide evidence for future research directions. Methods Relevant Chinese and English language literatures published from January 2014 to December 2024 were retrieved from the Web of Science (WOS) and China National Knowledge Infrastructure (CNKI) databases. CiteSpace and VOSviewer were used to conduct visual analyses of annual publication trends, core research institutions, author collaboration networks, keyword co-occurrence and clustering, burst keywords, and co-cited references. Results A total of 1 341 English publications and 319 Chinese publications were included. The annual number of publications in both Chinese and English showed an upward trend, with a more pronounced increase observed in English publications. Network analysis based on English literature revealed a closely connected multi-institutional collaboration network led by several core researchers, whereas Chinese studies were mainly characterized by small-team collaborations. After excluding search terms, the top three keywords by centrality in English publications were obesity, metabolic syndrome, and insulin resistance, while those in Chinese publications were hepatic fibrosis, childhood obesity, and insulin resistance. Keyword clustering of both Chinese and English publications indicated that research hotspots were mainly concentrated on childhood obesity, metabolic syndrome, noninvasive diagnostic techniques, and genetic mechanisms. Noninvasive imaging techniques and composite biomarkers have emerged as recent research frontiers. Conclusions Research on the diagnosis of NAFLD/MAFLD in children and adolescents has developed a framework centered on obesity-metabolic dysregulation-liver injury. Current trends focus primarily on improving noninvasive diagnostic technologies and comprehensively assessing multisystem metabolic health. These findings provide evidence to support the development of multidimensional pediatric diagnostic criteria, the integration of multicenter data, and the establishment of a life-course health management system.

关键词

非酒精性脂肪性肝病 / 代谢相关脂肪性肝病 / CiteSpace / VOSviewer / 可视化分析

Key words

non-alcoholic fatty liver disease / metabolic-associated fatty liver disease / CiteSpace / VOSviewer / bibliometric analysis

[1] Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease[J]. Lancet, 2021, 397(10290): 2212-2224.
[2] Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement[J].J Hepatol, 2020, 73(1): 202-209.
[3] World Health Organization. Obesity and overweight[EB/OL].(2024-03-01)[2024-03-27]. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
[4] Le Garf S, Nègre V, Anty R, et al. Metabolic fatty liver disease in children: A growing public health problem[J]. Biomedicines, 2021, 9(12): 1915.
[5] Bozic D, Podrug K, Mikolasevic I, et al. Ultrasound methods for the assessment of liver steatosis: A critical appraisal[J]. Diagnostics, 2022, 12(10): 2287.
[6] Yoneda M, Nakajima A. The role of MRI technology in liver evaluation for NAFLD patients: Advancements and opportunities[J]. Hepatology, 2023, 78(4): 1020-1022.
[7] Desai NK, Harney S, Raza R, et al. Comparison of controlled attenuation parameter and liver biopsy to assess hepatic steatosis in pediatric patients[J]. J Pediatr, 2016, 173: 160-164.e1.
[8] Mokhnacheva YV, Tsvetkova VA. Development of bibliometrics as a scientific field[J]. Sci Tech Inf Process, 2020, 47(3): 158-163.
[9] Garfield E. 100 citation classics from the Journal of the American Medical Association[J]. JAMA, 1987, 257(1): 52-59.
[10] Zhang L, El-Shabrawi M, Baur LA, et al. An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease[J]. Med, 2024, 5(7): 797-815.e2.
[11] Yodoshi T. Exploring non-invasive diagnostics and non-imaging approaches for pediatric metabolic dysfunction-associated steatotic liver disease[J]. World J Gastroenterol, 2024, 30(47): 5070-5075.
[12] Shumbayawonda E, Beyer C, de Celis Alonso B, et al. Reference range of quantitative MRI metrics corrected T1 and liver fat content in children and young adults: Pooled participant analysis[J]. Children, 2024, 11(10): 1230.
[13] Joshi M, Dillman JR, Singh K, et al. Quantitative MRI of fatty liver disease in a large pediatric cohort: Correlation between liver fat fraction, stiffness, volume, and patient-specific factors[J]. Abdom Radiol, 2018, 43(5): 1168-1179.
[14] Zhang S, Du T, Zhang J, et al. The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease[J]. Lipids Health Dis, 2017, 16(1): 15.
[15] Xuan Y, Wu D, Zhang Q, et al. Elevated ALT/AST ratio as a marker for NAFLD risk and severity: Insights from a cross-sectional analysis in the United States[J]. Front Endocrinol, 2024, 15: 1457598.
[16] Sandhu B, Perez Matos MC, Tran S, et al. Quantitative digital pathology reveals association of cell-specific PNPLA3 transcription with NAFLD disease activity[J]. JHEP Rep, 2019, 1(3): 199-202.
[17] Neri CR, Scapaticci S, Chiarelli F, et al. Liver steatosis: A marker of metabolic risk in children[J]. Int J Mol Sci, 2022, 23(9): 4822.
[18] Zou Y, Dai Y, Chen H, et al. MAFLD outperforms NAFLD in identifying metabolic dysfunction in U.S. adolescents: A NHANES 2017-2020 analysis[J]. BMC Gastroenterol, 2025, 25(1): 617.
[19] Nobili V, Alisi A, Newton KP, et al. Comparison of the phenotype and approach to pediatric vs adult patients with nonalcoholic fatty liver disease[J]. Gastroenterology, 2016, 150(8): 1798-1810.
[20] Peng T, Yi X, Lin Y, et al. Controlled attenuation parameter (CAP): The clinical value based on MRI-PDFF in children with obesity[J]. J Pediatr Endocrinol Metab, 2024, 37(7): 605-612.
[21] 刘婷婷, 林妍冰, 汪珊, 等. 超声衰减参数成像评价儿童代谢相关脂肪性肝病的价值[J/OL]. 中华医学超声杂志(电子版), 2023, 20(8): 787-794.
Liu TT, Lin YB, Wang S, et al. Evaluation of metabolic dysfunction-associated fatty liver disease in children by ultrasound-guided attenuation parameter[J/OL]. Chin J Med Ultrasound(Electron Ed), 2023, 20(8): 787-794. (in Chinese)
[22] Zeng J, Jin Q, Yang J, et al. Prevalence and incidence of MAFLD and associated anthropometric parameters among prepubertal children of the Shanghai Birth Cohort[J]. Hepatol Int, 2023, 17: 1416-1428.
[23] Jin BH, Wu ZY, Wang S, et al. Gender differences in non-alcoholic fatty liver disease in obese children and adolescents: A large cross-sectional study[J]. Hepatol Int, 2024, 18: 179-187.
[24] Liu WY, Eslam M, Zheng KI, et al. Associations of hydroxysteroid 17-beta dehydrogenase 13 variants with liver histology in Chinese patients with metabolic-associated fatty liver disease[J]. J Clin Transl Hepatol, 2021, 9(2): 194-202.
[25] Flisiak-Jackiewicz M, Bobrus-Chociej A, Wasilewska N, et al. From nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD)—New terminology in pediatric patients as a step in good scientific direction?[J]. J Clin Med, 2021, 10(5): 924.
[26] Yang A, Zhu X, Zhang L, et al. Non-invasive evaluation of NAFLD and the contribution of genes: An MRI-PDFF-based cross-sectional study[J]. Hepatol Int, 2022, 16(5): 1035-1051.
[27] Selvaraj EA, Mózes FE, Jayaswal ANA, et al. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis[J]. J Hepatol, 2021, 75(4): 770-785.
[28] Zeng F, Wang H, Li X. The defining of the reference range of liver stiffness and fat attenuation parameter for healthy Chinese children[J]. Eur J Gastroenterol Hepatol, 2021, 33(11): 1394-1399.
[29] Rigamonti AE, Bondesan A, Rondinelli E, et al. The role of aspartate transaminase to platelet ratio index (APRI) for the prediction of non-alcoholic fatty liver disease (NAFLD) in severely obese children and adolescents[J]. Metabolites, 2022, 12(2): 155.
[30] Zhu X, Sun F, Gao X, et al. Predictive value of triglyceride glucose index in non-obese non-alcoholic fatty liver disease[J]. BMJ Open, 2025, 15(4): e083686.
[31] John K, Franck M, Al Aoua S, et al. Non-invasive detection of fibrotic NASH in NAFLD patients with low or intermediate FIB-4[J]. J Clin Med, 2022, 11(15): 4394.
[32] Wang T, Zhang H, Wang K, et al. Development of a diagnostic model for MASLD and identification of daidzein as the potential drug using bioinformatics analysis and experiments[J]. Front Immunol, 2025, 16: 1698740.

基金资助

国家自然科学基金项目(81773421);江苏省医学创新团队项目(CXTDA2017035)