目的：量化评估非酒精性脂肪肝病(NAFLD)儿童、青少年肝内脂肪的临床意义。方法：对93例肥胖儿童、青少年进行形体学参数、肝功能、血脂、血糖及胰岛素释放试验和肝脏B超等检查，采用氢质子磁共振波谱定量测定肝内脂肪（IHF）含量，并按传统诊断标准将其分为单纯性肥胖组（31例）、非酒精性脂肪肝病-1组（NAFLD-1，33例）（B超示脂肪肝，但不伴有肝损）和NAFLD-2组（B超示脂肪肝，且伴有肝损，29例）。20例健康儿童、青少年作为正常对照组。观察IHF含量在组间的变化情况，分析IHF含量与各临床生化指标的相关关系以及探寻IHF量化改变的影响因素。结果：正常对照组、单纯性肥胖组、NAFLD-1组和NAFLD-2组IHF含量分别为0.80%（0.4%～1.0%）、2.9%（1.7%～4.3%）、14.0%（7.2%～17.5%）、18.8%（14.0%~29.1%），组间两两比较差异均有统计学意义（P<0.05）。单因素相关分析表明IHF含量与腰围、臀围、腰臀比、体重指数、收缩压、舒张压、丙氨酸氨基转移酶、门冬氨酸氨基转移酶、γ-谷氨酰转肽酶、空腹甘油三酯、低密度脂蛋白、口服葡萄糖耐量试验（OGTT）2 h血糖、空腹胰岛素、2 h胰岛素和胰岛素抵抗指数呈显著正相关，与高密度脂蛋白呈显著负相关。进一步的多元线性回归分析发现增加的腰围、降低的高密度脂蛋白水平和增高的OGTT 2 h血糖是IHF含量升高的独立危险因素。结论：IHF量化改变非常敏感，早期已增高于单纯性肥胖儿童、青少年，并随NAFLD的发生、发展进程而显著升高。量化的IHF与诸多临床生化指标相关，其中腰围、高密度脂蛋白和OGTT 2 h血糖是IHF含量的独立影响因素。
Abstract
OBJECTIVE: To quantitatively evaluate clinical significance of intrahepatic fat (IHF) content in children and adolescents with non-alcoholic fatty liver disease (NAFLD). METHODS: Ninety-three obese children were enrolled in this study. Physical parameters, liver function, serum lipids, glycemic and insulin related parameters were measured. Liver B-mode ultrasound (US) examination was performed. IHF content was quantified by 1H magnetic resonance spectroscopy (1H MRS). Three subgroups were classified according to the conditional diagnostic criteria for obese children: simple obesity (n=31), NAFLD-1 (US fatty liver and normal alanine aminotransterase, n=33) and NAFLD-2 (US fatty liver and elevated alanine aminotransterase, n=29). Twenty healthy age- and sex-matched children served as a control group. IHF content among the four groups was compared. The relationship of IHF content with other common clinical laboratory parameters and independent factors influencing increased IHF content were investigated. RESULTS: IHF content measured by 1H MRS was 0.80% (0.4%-1.0%), 2.9% (1.7%-4.30%), 14.0% (7.2%-17.5%) and 18.8% (14.0%-29.1%) respectively in the control, simple obese, NAFLD-1 and NAFLD-2 groups. There were significant differences in IHF content between the groups. Univariate correlation analysis demonstrated that IHF content was positively correlated with waist circumference, hip circumference, waisttohip ratio, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminoreansferase, γ-glutamic acid transtetase, triglyceride, low-density lipoprotein, OGTT 2-hour plasma glucose, fasting insulin, 2-hour insulin and insulin resisfence, and negatively correlated with high-density lipoprotein. Multivariate linear regression analysis demonstrated three independent risk factors for increased IHF content: increased waist circumference, increased 2-hour plasma glucose and decreased high-density lipoprotein levels. CONCLUSIONS: IHF content determined by 1H MRS can reflect early hepatic fatty infiltration and is closely related to the occurrence and progress of NAFLD in obese children and adolescents. There is a significant correlation between most of common clinical laboratory parameters and IHF content, and waist circumference, high-density lipoprotein and OGTT 2-hour plasma glucose are independent factors impacting IHF content.
关键词
肝内脂肪 /
氢质子磁共振波谱 /
非酒精性脂肪肝病 /
肥胖 /
儿童 /
青少年
Key words
Intrahepatic fat /
1H Magnetic resonance spectroscopy /
Nonalcoholic fatty liver disease /
Obesity /
Child /
Adolescent
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］Grant LM, LiskerMelman M. Nonalcoholic fatty liver disease［J］. Ann Hepatol, 2004, 3(3): 93-99.
［2］Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years［J］. Hepatology, 1990, 11(1): 74-80.
［3］Carter- Kent C, Brunt EM, Yerian LM, Alkhouri N, Anqulo P, Kohli R, et al. Relations of steatosis type, grade, and zonality to histological features in pediatric nonalcoholic fatty liver disease ［J］. J Pediatr Gastroenterol Nutr, 2011, 52(2):190-197.
［4］李辉，季成叶，宗心南，张亚钦. 中国0～18岁儿童、青少年体块指数的生长曲线［J］. 中华儿科杂志，2009，47（7）：493-498.
［5］中华医学会肝脏病学分会脂肪肝和非酒精性肝病学组. 非酒精性脂肪肝病诊疗指南［J］. 中华肝脏病杂志，2006，14（3）：161-163.
［6］Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling［J］. Diabetes Care, 2004, 27(6): 1487-1495.
［7］Longo R, Pollesello P, Ricci C, Masutti F, Kvam BJ, Bercich L, et al. Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis ［J］. J Magn Reson Imaging, 1995, 5(3): 281-285.
［8］Metha SR, Thomas EL, Patel N, Crofton ME, McCarthy J, Eliahoo J, et al. Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification［J］. Hepatol Res, 2010, 40(4): 399-406.
［9］Cowin GJ, Jonsson JR, Bauer JD, Ash S, Ali A, Osland EJ, et al. Magnetic Resonance Imaging and spectroscopy for monitoring liver steatosis［J］. J Magn Reson Imaging, 2008, 28(4): 937-945.
［10］Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population［J］. Am J Physiol Endocrinol Metab, 2005, 288(2): E462-E468.
［11］Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K,Bergholm R, Johansson LM, et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors［J］. Gastroenterology, 2009, 137(3): 865-872.
［12］Larson-Meyer DE, Newcomer BR, VanVrancken-Tompkins CL, Sothern M. Feasibility of assessing liver lipid by proton magnetic resonance spectroscopy in healthy normal and overweight prepubertal children［J］. Diabetes Technol Ther, 2010, 12(3): 207-212.
［13］Zhang H, Peng Y, Liu Z, Li S, Lv Z, Tian L, et al. Effects of acupuncture therapy on abdominal fat and hepatic fat content in obese children: a magnetic resonance imaging and proton magnetic resonance spectroscopy study［J］. J Altern Complement Med, 2011, 17(5): 413-420.
［14］Ma X, Holalkere NS, Kambadakone RA, Mino-Kenudson M, Hahn PF, Sahani DV. Imaging-based quantification of hepatic fat: methods and clinical applications［J］. Radiographics, 2009, 29(5): 1253-1277.
［15］Thomas EL, Hamilton G, Patel N, O′Dwyer R, Doré CJ, Goldin RD, et al. Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study［J］. Gut, 2005, 54(1): 122-127.
［16］Cali AM, De Oliveira AM, Kim H, Chen S, ReyesMugica M, Escalera S, et al. Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link?［J］. Hepatology, 2009, 49(6): 1896-1903.
［17］Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk［J］. World J Gastroenterol, 2011, 17(26): 3082-3091.
［18］Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease［J］. Circulation, 2008, 118(3): 277-283.
PDF(998 KB)
