婴儿肝炎综合征患儿血清高尔基体糖蛋白73表达的临床意义

Expression and clinical significance of serum Golgi protein 73 in infantile hepatitis syndrome

目的探讨不同病因所致婴儿肝炎综合征（IHS）患儿血清高尔基体糖蛋白73（GP73）的表达及其可能的临床意义。方法选取2012年2－12月于广州市妇女儿童医疗中心就诊的IHS患儿79例，其中胆道闭锁组15例，感染组29例，Citrin缺陷致新生儿肝内胆汁淤积症（NICCD）组5例，不明病因组30例。同期体检健康婴儿30例为健康对照组。采用酶联免疫吸附试验（ELISA）检测血清GP73水平，用免疫比浊法对血液标本的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、结合胆红素（DBIL）、碱性磷酸酶（ALP）、γ-谷氨酰转移酶（γ-GT）、总胆汁酸（TBA）和清蛋白（ALB）进行检测，并进行相应的统计学分析。结果胆道闭锁组、感染组、NICCD组、不明病因组和健康对照组血清中GP73水平分别为（296.6±67.5） μg/L、（185.1±66.4） μg/L、（199.2±87.1） μg/L、（181.7±74.2） μg/L和（65.3±17.0） μg/L，γ-GT水平分别为（764.7±775.8） U/L、（448.2±352.7） U/L、（239.4±88.7） U/L、（283.3±377.2） U/L和（54.0±72.6） U/L。IHS患儿血清GP73及γ-GT水平均高于健康对照组，其中胆道闭锁组最高，差异有统计学意义（F＝46.775、9.238，均P〈0.05）。IHS患儿血清GP73水平与γ-GT呈正相关（r＝0.280，P〈0.05），与肝功能指标ALT、AST、TBIL、DBIL、ALP、TBA、ALB无相关性（r＝－0.061、－0.071、0.164、0.123、0.137、0.008、－0.047，均P〉0.05）。根据GP73及γ-GT血清水平制作受试者工作特征曲线，采用血清GP73诊断胆道闭锁的敏感性为80.0%，特异性为82.8%，曲线下面积（AUC）为0.872，而γ-GT敏感性和特异性分别为66.7%和71.9%，AUC为0.731。结论IHS患儿血清GP73水平均有升高，胆道闭锁患儿血清GP73水平升高更为显著；血清GP73在胆道闭锁诊断中的敏感性和特异性均高于γ-GT。可能对胆道闭锁与其他病因IHS的早期鉴别诊断有一定的参考价值。

Objective To investigate the expression and the possible clinical significance of serum Golgi protein （GP73） in infantile hepatitis syndrome（IHS） by different causes. Methods Totally 79 patients with IHS in Guangzhou Women and Children＇s Medical Center from February 2012 to December 2012 were enrolled in this study, including 15 cases with biliary atresia（BA） group,29 cases with infection（ infection group） ,5 cases with neonatal intrahepatic cholestasis caused by citrin deficiency （NICCD group） , and 30 cases with unknown etiology （idiopathic infantile hepatitis group）. At the same time ,30 healthy infants were enrolled as healthy control group. The serum levels of GP73 were de- termined by quantitative enzymelinked immunosorbent assay（ELISA） , and the children＇s liver function[ alanine aminotransferase （ ALT）, aspartate aminotransferase （ AST ）, total bilirubin （ TBIL ）, direct bilirubin （ DBIL ）, alkaline phosphatase （ALP） , γ - glutamyl trans - peptidase （ γ - GT） , total bile acid （TBA） and albumin （ ALB ） ] were measured by turbidimetric inhibition immuno assay. Then, the corresponding data were statistically analyzed. Results Serum GP73 in BA group, infection group, NICCD group, idiopathic infantile hepatitis group and the healthy control group were （296.6 ± 67.5） μg/L, （ 185. 1 ± 66.4 ） μg/L, （ 199.2 ± 87.1 ） μg/L, （ 181.7 ± 74.2 ） μg/L and （65.3 ± 17.0） μg/L, respectively. Serum γ - GT levels in BA group, infection group, NICCD group, idiopathic infantile hepatitis group and healthy control group were （764.7 ± 775.8 ） U/L, （448.2 ± 352.7 ） U/L, （ 239.4 ± 88.7 ） U/L, （283.3 ± 377.2） U/L and （54.0 ±72.6） U/L,respectively. The levels of GP73 and γ - GT were significantly higher in infants with IHS,and the levels of GP73 and γ -GT in infants with BA were the highest（ F = 46. 775,9. 238 ,all P 〈 0. 05 ）. There was a positive correlation between serum levels of GP73 and γ- GT （ r = 0. 280, P 〈 0.05 ） , and there was no correlation between GP73 and ALT, AST, TBIL, DBIL, ALP, TBA, ALB （ r = - 0. 061, - 0. 071 ,0. 164,0. 123,0. 137, 0. 008, - 0. 047, respectively, all P 〉 0.05 ）. The receiver operating characteristic curve （ ROC ） constructed with GP73showed a sensitivity of 80.0% and specificity of 82.8% with an area under the receiver（AUC） of 0.872 for diagnosis of BA,comparatively,a sensitivity of 66.7% and specificity of 71.9% were showed with a AUC of 0. 731 when performed with γ- GT. Conclusions Serum GP73 concentration significantly increased in all liver disease groups,regardless of the etiology. Serum GP73 expression is significantly higher in infants with BA. Serum GP73 shows a superior sensitivity and specificity to γ- GT for diagnosis of BA, which might be useful for early diagnosis of BA and IHS with different causes.