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血清精氨酸琥珀酸裂解酶测定用于肝病诊断的研究

Study of serum argininosuccinate lyase determination for diagnosis of liver diseases.

作者信息

Feng Jia-fu, Chen Ting-mei, Wen Yang-an, Wang Jian, Tu Zhi-guang

机构信息

Key Laboratory of Laboratory Medical Diagnosis of Education Ministry, Faculty of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

出版信息

J Clin Lab Anal. 2008;22(3):220-7. doi: 10.1002/jcla.20245.

Abstract

The objectives of this research were to establish an automatic analysis method for the determination of serum argininosuccinate lyase (ASL) and to investigate the value of serum ASL test in the diagnosis of various liver disorders. According to the chemical reaction catalyzed by ASL, an enzyme-coupled reaction system was designed, and a methodology evaluation of this method was performed. A total of 291 patients with various liver diseases, 247 patients with nonliver disease and 32 healthy controls, were recruited, their serum levels of ASL and traditional hepatopathy markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and total bilirubin (TBil), were all determined, and their diagnostic values in liver diseases were analyzed and compared. Liver biopsy and the score of histopathological inflammation grading were performed in 31 patients with hepatopathy to explore the correlation between serum ASL level and hepatic histopathological change. A continuous monitoring assay method of serum ASL activity was established, which could be performed with automatic biochemistry analyzer. Methodological evaluation exhibited that the precision of this method was good indicated by the 4.0% intraassay coefficient of variation (CV), and 5.9% interassay CV. The mean recovery was 100.5%, linear range was from 0 to 167.7 U/L, and the lowest detection limit was approximately 0 U/L. All of the tested hepatopathy markers listed above were significantly increased in the liver disease group. However, levels of traditional markers of hepatopathy were all significantly increased at different degrees (all P<0.001) in patients with nonliver diseases; in contrast, there were no significantly increased ASL levels in all non-hepatopathy groups (P=0.335). The receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of ASL were 100% and 91.1% (cutoff value=8 U/L), respectively, in the assessment of liver diseases. In contrast, ALT levels were 97.6% and 24.7%, and AST levels were 83.8% and 28.3% (both cutoff values=40.0 U/L), respectively. A positive correlation (r=0.417, P=0.019) was observed between serum ASL levels (86.9+/-26.5) and scores of histopathological inflammation grading (SHIG) (9.83+/-3.36). The sensitivity and specificity of ALS is much higher than that of ALT and AST for the diagnosis of liver diseases. ASL may be a more valuable marker for estimating hepatopathy.

摘要

本研究的目的是建立一种自动分析方法来测定血清精氨酸琥珀酸裂解酶(ASL),并探讨血清ASL检测在各种肝脏疾病诊断中的价值。根据ASL催化的化学反应,设计了一种酶联反应体系,并对该方法进行了方法学评价。共招募了291例各种肝脏疾病患者、247例非肝脏疾病患者和32例健康对照者,测定了他们血清中的ASL水平以及传统肝病标志物,包括丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(GGT)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)和总胆红素(TBil),并分析比较了它们在肝脏疾病中的诊断价值。对31例肝病患者进行了肝活检和组织病理学炎症分级评分,以探讨血清ASL水平与肝脏组织病理学变化之间的相关性。建立了一种血清ASL活性的连续监测测定方法,可使用自动生化分析仪进行检测。方法学评价表明,该方法的精密度良好,批内变异系数(CV)为4.0%,批间CV为5.9%。平均回收率为100.5%,线性范围为0至167.7 U/L,最低检测限约为0 U/L。上述所有检测的肝病标志物在肝病组中均显著升高。然而,非肝脏疾病患者中传统肝病标志物水平均有不同程度的显著升高(均P<0.001);相比之下,所有非肝病组中ASL水平均无显著升高(P=0.335)。受试者工作特征(ROC)曲线显示,在肝脏疾病评估中,ASL的敏感性和特异性分别为100%和91.1%(临界值=8 U/L)。相比之下,ALT水平分别为97.6%和24.7%,AST水平分别为83.8%和28.3%(临界值均=40.0 U/L)。血清ASL水平(86.9±26.5)与组织病理学炎症分级评分(SHIG)(9.83±3.36)之间存在正相关(r=0.417,P=0.019)。在肝脏疾病诊断中,ALS的敏感性和特异性远高于ALT和AST。ASL可能是评估肝病更有价值的标志物。

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