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血氨及胆碱酯酶对肝硬化伴轻微肝性脑病的早期诊断价值
DOI: 10.3969/j.issn.1001-5256.2023.02.013
伦理学声明：本研究方案于2021年9月1日经由宁夏医科大学医院伦理委员会审批，批号：KYLL-2021-841，在中国临床试验注册中心注册(注册号：ChiCTR2100050880)，患者均签署知情同意书。
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：王晓东、丁向春负责设计研究方案并提供指导性支持；杨旭宏、王明磊、刘文潇负责样本收集及分析；王敏行、马万龙数据整理分析; 杨旭宏、杨勇负责论文的撰写与修改。
Value of blood ammonia and cholinesterase in the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy
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摘要:
目的 探讨血清标志物对肝硬化合并轻微型肝性脑病(MHE)的早期诊断价值。 方法 前瞻性纳入2020年4月—2022年2月于宁夏医科大学总医院住院治疗，并经临床表现、实验室检查、影像学检查或肝穿刺活检确诊为乙型肝炎肝硬化患者81例。根据数字连接试验A(NCT-A)和数字符号试验(DST)分为单纯肝硬化组45例、MHE组36例。检测肝功能(ALT、AST、GGT、ALP和TBil)、白蛋白、血氨、胆碱酯酶和凝血酶原时间。计数资料2组间比较采用χ2检验；正态分布的计量资料2组间比较采用独立样本t检验；非正态分布的计量资料2组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H检验。使用Logistic回归和受试者工作特征曲线下面积(AUC)分析MHE的预测因素。 结果 与单纯肝硬化组相比，MHE组NCT-A量表评分升高(Z=-7.110, P＜0.001)，DST量表评分降低(t=12.223, P＜0.001)，差异均有统计学意义。单因素分析显示，AST、白蛋白、凝血酶原时间、胆碱酯酶和血氨在MHE患者中显著改变(Z值分别为-2.319、-2.643、-1.982、-6.594、-5.331，P值均＜0.05)；但在多变量分析中，只有胆碱酯酶和血氨水平是显著的预测因子(P值均＜0.05)，并且它们与Child-Pugh评分分级相关(P值均＜0.05)。胆碱酯酶、血氨以及两者联合诊断MHE的AUC值分别为0.925、0.845和0.941，最佳截断值分别为2966、60和0.513。 结论 血氨、胆碱酯酶及两者联合检测对肝硬化合并MHE的早期诊断具有潜在的临床价值。 Abstract:Objective To investigate the value of serum markers in the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE). Methods A prospective analysis was performed for 81 patients who were hospitalized and treated in General Hospital of Ningxia Medical University from April 2020 to February 2022, and all these patients were diagnosed with hepatitis B cirrhosis based on clinical manifestation, laboratory examination, and radiological examination or liver biopsy. According to digital connection test A (NCT-A) and digital symbol test (DST), these patients were divided into simple cirrhosis group with 45 patients and MHE group with 36 patients. Related indices were measured, including liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBil)], albumin, blood ammonia, cholinesterase, and prothrombin time. The independent samples t-test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The logistic regression analysis and the area under the ROC curve (AUC) were used to investigate the predictive factors for MHE. Results Compared with the simple cirrhosis group, the MHE group had a significant increase in NCT-A score (Z=-7.110, P < 0.001) and a significant reduction in DST score (t=12.223, P < 0.001). The univariate analysis showed that there were significant changes in AST, albumin, prothrombin time, cholinesterase, and blood ammonia in the patients with MHE (Z=-2.319, -2.643, -1.982, -6.594, and -5.331, all P < 0.05), while the multivariate analysis showed that only cholinesterase and blood ammonia were significant predictive factors (all P < 0.05) and were correlated with Child-Pugh score (all P < 0.05). Cholinesterase, blood ammonia, and their combination had an AUC of 0.925, 0.845, and 0.941, respectively, in the diagnosis of MHE, with an optimal cut-off value of 2966, 60, and 0.513, respectively. Conclusion Blood ammonia, cholinesterase, and their combined measurement have a potential clinical value in the early diagnosis of liver cirrhosis with MHE. -
Key words:
- Liver Cirrhosis /
- Hepatic Encephalopathy /
- Hyperammonemia /
- Cholinesterases /
- Early Diagnosis
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表 1 肝硬化组及MHE组患者的一般资料比较
Table 1. General information of liver cirrhosis and MHE group
项目 肝硬化组(n=45) MHE组(n=36) 统计值 P值 男/女(例) 30/15 23/13 χ2=0.068 0.749 年龄(年) 48.5±8.5 50.3±9.7 t=-0.856 0.395 教育水平(年) 7.8±1.8 7.7±1.9 t=0.335 0.738 NCT-A(s) 39.5(32.8~44.8) 70.7(60.2~84.6) Z=-7.110 0.001 DST(分) 43.0±9.8 21.2±4.7 t=12.223 0.001 ALT(U/L) 89.5(41.9~126.0) 50.5(78.9~130.1) Z=-0.033 0.973 AST(U/L) 64.6(43.0~87.8) 90.9(52.1~125.1) Z=-2.319 0.020 GGT(U/L) 67.8(60.4~111.0) 66.4(29.6~130.9) Z=-0.718 0.473 ALP(U/L) 114.8(75.8~161.7) 104.4(71.0~155.5) Z=-0.661 0.509 TBil(μmol/L) 78.9(26.1~130.2) 83.5(57.3~133.1) Z=-0.932 0.352 白蛋白(g/L) 29.4(27.0~33.6) 26.9(23.5~29.6) Z=-2.643 0.008 血氨(μmol/L) 48(42~62) 64(69~80) Z=-5.331 0.001 凝血酶原时间(s) 16.8(14.5~17.9) 17.9(15.9~18.9) Z=-1.982 0.047 胆碱酯酶(U/L) 3567(3274~4148) 2399(2024~2781) Z=-6.594 0.001 
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表 2 单变量和多变量分析的诊断效能
Table 2. Diagnostic efficacy of univariate and multivariate analysis
变量 截断值 AUC 敏感度(%) 特异度(%) 约登指数 胆碱酯酶 ＜2966 0.925 86.1(70.5~95.3) 91.1(78.8~97.5) 0.772 血氨 ＞60 0.845 94.4(81.3~99.3) 75.6(60.5~87.1) 0.700 胆碱酯酶+血氨 ＞0.513 0.941 91.7(77.5~98.2) 84.4(70.5~93.5) 0.761
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表 3 MHE和肝硬化患者Child-Pugh分级分析
Table 3. Child-Pugh grading analysis of patients with minimai hepatic encephalopathy and cirrhosis
统计变量 Child-Pugh A级(n=35) Child-Pugh B级(n=25) Child-Pugh C级(n=21) 统计值 P值 男/女(例) 24/11 15/10 14/7 χ2=0.493 0.782 年龄(岁) 49(43~55) 52(56.5~39.5) 55(43~57.5) H=1.840 0.398 胆碱酯酶(U/L) 3790(3423~4432) 2980(2756~3153)1) 1966(2236~2521)1)2) H=69.813 0.01 血氨(μmol/L) 45(37~56) 46(41~71) 65(60~74)1)2) H=25.126 0.01 注：与Child-Pugh A级比较，1)P＜0.05；与Child-Pugh B级比较，2)P＜0.05。
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