Research advances in the diagnosis of nonalcoholic fatty liver disease in children
-
摘要: 非酒精性脂肪性肝病(NAFLD)已成为儿童最常见的慢性肝病之一,其临床表现缺乏特异性,目前诊断主要根据临床症状结合辅助检查。其中,血清肝脏酶谱、血脂谱、稳态模型胰岛素抵抗指数临床应用较多,而细胞角蛋白18、空腹甘油三酯血糖指数等有可能成为儿童NAFLD诊断的新指标。超声、MRI、CT等影像学检查对儿童NAFLD诊断均有局限性,但肝脏脂肪变性定量诊断技术和声辐射力脉冲弹性成像检测技术未来可能有较高应用价值。关于NAFLD的多种评分方法有待进一步研究验证。目前肝活组织检查仍为儿童NAFLD诊断的"金标准"。对儿童NAFLD最新研究进展进行总结,并对相关实验室指标及影像学检查的诊断价值加以讨论。Abstract: Nonalcoholic fatty liver disease ( NAFLD) has become one of the most common chronic liver diseases in children. Since the clinical manifestations of NAFLD lack specificity, the diagnosis of this disease is mainly based on clinical symptoms and auxiliary examinations.Serum liver enzymes, blood lipid levels and homeostasis model assessment of insulin resistance are commonly used in clinical practice, and cytokeratin-18, triglyceride glucose index may become new markers for the diagnosis of NAFLD in children. Imaging examinations such as ultrasound, magnetic resonance imaging and computed tomography have their own limitations in the diagnosis of NAFLD in children, while controlled attenuation parameter and acoustic radiation force impulse may have a high value in future. The scoring systems for NAFLD need to be validated by clinical research. At present, liver biopsy remains the“gold standard”for the diagnosis of NAFLD in children. This article summarizes the latest research advances in NAFLD in children and discusses the diagnostic values of laboratory markers and imaging examinations.
-
Key words:
- fatty liver /
- diagnosis /
- child /
- review
-
[1]Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association.Guidelines for Management of non-alcoholic fatty liver disease[J].J Clin Hepatol, 2010, 26 (2) :120-124. (in Chinese) 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].临床肝胆病杂志, 2010, 26 (2) :120-124. [2]TEMPLE JL, CORDERO P, LI J, et al.A guide to non-alcoholic fatty liver disease in childhood and adolescence[J].Int J Mol Sci, 2016, 17 (6) :e947. [3]ANDERSON EL, HOWE LD, JONES HE, et al.The prevalence of non-alcoholic fatty liver disease in children and adolescents:a systematic review and meta-analysis[J].PLo S One, 2015, 10 (10) :e0140908. [4]FAN JG.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China[J].J Gastroenterol Hepatol, 2013, 28 (1) :11-17. [5]LU ZY, SHAO Z, LI YL, et al.Prevalence of and risk factors for non-alcoholic fatty liver disease in a Chinese population:an 8-year follow-up study[J].World J Gastroenterol, 2016, 22 (13) :3663-3669. [6]MIRTA C, MARGARITA R, FERNANDO.Non-alcoholic fatty liver disease:a new epidemic in children[J].Arch Argent Pediatr, 2016, 114 (6) :563-569. [7]OH MS, KIM S, JANG JH, et al.Associations among the degree of nonalcoholic fatty liver disease, metabolic syndrome, degree of obesity in children, and parental obesity[J].Pediatr Gastroenterol Hepatol Nutr, 2016, 19 (3) :199-206. [8]CRUZ MA, CRUZ JF, MACENA LB, et al.Association of the nonalcoholic hepatic steatosis and its degrees with the values of liver enzymes and homeostasis model assessment-insulin resistance index[J].Gastroenterology Res, 2015, 8 (5) :260-264. [9]BHATT SP, MISRA A, NIGAM P, et al.Phenotype, body composition, and prediction equations (indian fatty liver index) for non-alcoholic fatty liver disease in non-diabetic asian indians:a case-control study[J].PLo S One, 2015, 10 (11) :e0142260. [10]NOBILI V, REALE A, ALISI A, et al.Elevated serum ALT in children presenting to the emergency unit:relationship with NAFLD[J].Dig Liver Dis, 2009, 41 (10) :749-752. [11]OBIKA M, NOGUCHI H.Diagnosis and evaluation of nonalcoholic fatty liver disease[J].Exp Diabetes Res, 2012, 2012:145754. [12]YANG MH, SUNG J, GWAK GY.The associations between apolipoprotein B, A1, and the B/A1 ratio and nonalcoholic fatty liver disease in both normal-weight and overweight Korean population[J].J Clin Lipidol, 2016, 10 (2) :289-298. [13]CLAIRE LM, SILVA A, WAYNE C, et al.Insulin resistance in children:consensus, perspective, and future directions[J].J Clin Endocrinol Metab, 2010, 95 (12) :5189-5198. [14]GUERRERO-ROMERO F, VILLALOBOS-MOLINA R, JIMNEZ-FLORES JR, et al.Fasting triglycerides and glucose index as a diagnostic test for insulin resistance in young adults[J].Arch Med Res, 2016, 47 (5) :382-387. [15]ZHANG S, DU T, ZHANG J, et al.The triglyceride and glucose index (Ty G) is an effective biomarker to identify nonalcoholic fatty liver disease[J].Lipids Health Dis, 2017, 16 (1) :15. [16]YANG ZH, YANG SX, QIN CZ, et al.Clinical values of elevated serum cytokeratin-18 levels in hepatitis:a meta-analysis[J].Hepat Mon, 2015, 15 (5) :e25328. [17]KRAMER G, ERDAL H, MERTENS HJ, et al.Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18[J].Cancer Res, 2004, 64 (5) :1751-1756. [18]VANESSA JL, STPHANIE B, STPHANIE P, et al.Serum markers of hepatocyte death and apoptosis are non invasive biomarkers of severe fibrosis in patients with alcoholic liver disease[J].PLo S One, 2011, 6 (3) :e17599. [19]FITZPATRICK E, MITRY RR, QUAGLIA A, et al.Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD[J].J Pediatr Gastroenterol Nutr, 2010, 51 (4) :500-506. [20]TARANTINO G, MAZZARELLA C, TARANTINO M, et al.Could high levels of tissue polypeptide specific antigen, a marker of apoptosis detected in nonalcoholic steatohepatitis, improve after weight loss?[J].Dis Markers, 2009, 26 (2) :55-63. [21]HUANG Q, YU J, ZHANG X, et al.Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease[J].Biomed Rep, 2016, 5 (2) :188-192. [22]CARDOSO AS, GONZAGA NC, MEDEIROS CC, et al.Association of uric acid levels with components of metabolic syndrome and non-alcoholic fatty liver disease in overweight or obese children and adolescents[J].J Pediatr (Rio J) , 2013, 89 (4) :412-418. [23]HAMZA RT, ELFARAMAWY AA, MAHMOUD NH.Serum Pentraxin3 fragment as a noninvasive marker of nonalcoholic fatty liver disease in obese children and adolescents[J].Horm Res Paediatr, 2016, 86 (1) :11-20. [24]SHIMOMURA Y, TAKAKI A, WADA N, et al.The serum oxidative/anti-oxidative stress balance becomes dysregulated in patients with non-alcoholic steatohepatitis associated with hepatocellular carcinoma[J].Intern Med, 2017, 56 (3) :243-251. [25]POLYZOS SA, KOUNTOURAS J, MANTZOROS CS.Adipokines in nonalcoholic fatty liver disease[J].Metabolism, 2016, 65 (8) :1062-1079. [26]CHISHIMA S, KOGISO T, MATSUSHITA N, et al.The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease[J].Intern Med, 2017, 56 (5) :473-480. [27]HAN MA, SAOUAF R, AYOUB W, et al.Magnetic resonance imaging and transient elastography in the management of nonalcoholic fatty liver disease (NAFLD) [J].Expert Rev Clin Pharmacol, 2017, 10 (4) :379-390. [28]LIU XL, PAN Q, ZHANG RN, et al.Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population[J].World J Gastroenterol, 2016, 22 (44) :9844-9852. [29]DONG QY, XIN YN, XUAN SY.Advances in GCKR polymorphisms and non-alcoholic fatty liver disease[J/CD].Chin J Liver Dis:Electronic Edition, 2015, 7 (4) :22-25. (in Chinese) 董全勇, 辛永宁, 宣世英.葡萄糖激酶调节蛋白基因多态性与非酒精性脂肪性肝病相关性的研究进展[J/CD].中国肝脏病杂志:电子版, 2015, 7 (4) :22-25. [30]PETJEM, YKI-JRVINEN H.Definitions of normal liver fat and the association of insulin sensitivity with acquired and genetic NAFLD-A systematic review[J].Int J Mol Sci, 2016, 17 (5) :e633. [31]ZHANG HX, YANG HP, LAI C, et al.Diagnostic value of ultrasonographic examination for hepatic steatosis in obese children[J].Chin J Contemp Pediatr, 2014, 16 (9) :873-877. (in Chinese) 张洪锡, 杨会萍, 赖灿, 等.超声筛检肥胖儿童脂肪肝的价值评估[J].中国当代儿科杂志, 2014, 16 (9) :873-877. [32]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. [33]GAO Y, TANG Y, WANG Q, et al.Acoustic radiation force impulse imaging in measurement of liver elasticity in normal children[J].Chin J Med Imaging Technol, 2014, 30 (12) :1865-1868. (in Chinese) 高洋, 唐毅, 王荞, 等.声脉冲辐射力弹性成像技术检测正常儿童肝脏弹性[J].中国医学影像技术, 2014, 30 (12) :1865-1868. [34]FIERBINTEANU BC, SPOREA I, PANAITESCU E, et al.Value of acoustic radiation force impulse imaging elastography for non-invasive evaluation of patients with nonalcoholic fatty liver disease[J].Ultrasound Med Biol, 2013, 39 (11) :1942-1950. [35]KAMBLE R, SODHI KS, THAPA BR, et al.Liver acoustic radiation force impulse (ARFI) in childhood obesity:comparison and correlation with biochemical markers[J].J Ultrasound, 2016, 20 (1) :33-42. [36]KLEINER DE, BRUNT EM, van NATTA M, et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease[J].Hepatology, 2005, 41 (6) :1313-1321. [37]XIN FZ, FAN JG.Brief introduction of european clinical practice guidelines for the management of patients with non-alcoholic fatty liver diseases[J].J Pract Hepatol, 2016, 19 (4) :7-8. (in Chinese) 信丰智, 范建高.欧洲非酒精性脂肪性肝病诊疗指南简介[J].实用肝脏病杂志, 2016, 19 (4) :7-8. [38]NOBILI V, ALISI A, VANIA A, et al.The pediatric NAFLD fibrosis index:a predictor of liver fibrosis in children with non-alcoholic fatty liver disease[J].BMC Med, 2009, 7:21. [39]YANG HR, KIM HR, KIM MJ, et al.Noninvasive parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease[J].World J Gastroenterol, 2012, 18 (13) :1525-1530. [40]ALKHOURI N, MANSOOR S, GIAMMARIA P, et al.The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease[J].PLo S One, 2014, 9 (8) :e104558. [41]XU ZJ, LU LG.Types and clinical manifestations of nonalcoholic fatty liver disease[J].Mod Digest Interv, 2009, 14 (3) :173-175. (in Chinese) 徐正婕, 陆伦根.非酒精性脂肪性肝病的类型和临床表现[J].现代消化及介入诊疗, 2009, 14 (3) :173-175. [42]ZHU SS, WANG LM.Diagnosis and treatment of non-alcoholic fatty liver disease in children[J].Chin J Pract Pediatr, 2015, 30 (5) :336-339. (in Chinese) 朱世殊, 王丽旻.儿童非酒精性脂肪性肝病的诊治[J].中国实用儿科杂志, 2015, 30 (5) :336-339.
本文二维码
计量
- 文章访问数: 2577
- HTML全文浏览量: 34
- PDF下载量: 408
- 被引次数: 0