经活检证实的非酒精性脂肪性肝病患儿循环中连蛋白增加。
Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease.
作者信息
Pacifico Lucia, Bonci Enea, Marandola Lidia, Romaggioli Sara, Bascetta Stefano, Chiesa Claudio
机构信息
Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
出版信息
World J Gastroenterol. 2014 Dec 7;20(45):17107-14. doi: 10.3748/wjg.v20.i45.17107.
AIM
To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD).
METHODS
A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue.
RESULTS
Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P < 0.01]. In patients with NAFLD, zonulin concentrations increased significantly with the severity of steatosis and the Spearman's coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P < 0.05); however, we did not find a significant correlation between zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance.
CONCLUSION
Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.
目的
研究循环中连蛋白与经活检确诊为非酒精性脂肪性肝病（NAFLD）的肥胖儿童肝病分期之间的潜在关联。
方法
进行了一项病例对照研究。病例为40名患有NAFLD的肥胖儿童。NAFLD的诊断基于肝脏脂肪分数高（HFF≥5%）的磁共振成像（MRI），并经肝活检证实，≥5%的肝细胞含有大泡性脂肪。对照组选自转氨酶水平正常、无脂肪肝MRI证据以及无其他慢性肝病病因的肥胖儿童。对照组与病例在年龄、性别、青春期阶段以及体重指数标准差评分上尽可能匹配（1:1）。所有参与者均接受了临床检查、实验室检测，包括连蛋白、炎症和代谢参数检测，以及用于测量HFF和内脏脂肪组织的MRI检查。
结果
患有NAFLD的肥胖受试者的连蛋白值显著高于无NAFLD的受试者[中位数（四分位间距），4.23（3.18 - 5.89）对3.31（2.05 - 4.63），P < 0.01]。在NAFLD患者中，连蛋白浓度随脂肪变性严重程度显著增加，Spearman系数显示连蛋白值与脂肪变性之间呈正相关（r = 0.372，P < 0.05）；然而，我们未发现连蛋白与小叶炎症（P = 0.23）、气球样变（P = 0.10）、纤维化评分（P = 0.18）或非酒精性脂肪性肝炎的存在（P = 0.17）之间存在显著相关性。在整个研究人群中，在对年龄、性别和青春期状态进行调整后，连蛋白水平与γ-谷氨酰转移酶、2小时胰岛素、HFF呈正相关，与全身胰岛素敏感性指数（WBISI）呈负相关。当将这些关联限制在NAFLD患者组时，2小时胰岛素、肝脂肪和WBISI仍具有统计学意义。
结论
患有NAFLD的儿童和青少年循环中连蛋白增加，且与脂肪变性的严重程度相关。
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