肝硬化合并骨密度紊乱患者实验室证候及其星座部分参数变化的诊断价值、预测价值及似然比

N. Drobinska, O. Abrahamovych, M. Abrahamovych, O. Fayura, M. Ferko, I. Korniychuk, R. Ivanochko
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Materials and methods. 90 patients with LC (27 women, 30.0 %), 63 men (70.0 %),18–66 years of age were randomly examined and stratified for bone lesions according to the T-score in accordance with WHO recommendations. 72 (80.0 %) patients combining LC with DBMD formed a research group (RG), out of which: 46 (63.9 %) patients combined LC with osteopenia (RG-A); 26 (36.1 %) patients combined LC with osteoporosis (RG-B). 18 (20.0 %) patients with LC without DBMD formed a comparison group (CG). Laboratory syndromes were diagnosed on the basis of abnormalities detection in laboratory blood parameters, namely: cytolysis – in the case of increased levels of aspartate aminotransferase or alanine aminotransferase in blood plasma; mesenchymal-inflammatory syndrome – increased thymol test or gamma-globulins; hepatocellular insufficiency – decreased fibrinogen or prothrombin indeces, or total protein, or albumin; cholestasis – increased alkaline phosphatase (AP), or gamma-glutamyltranspeptidase or total bilirubin; portosystemic shunting – decreased sodium or potassium, or increased creatinine indeces; dyslipidemia – increased cholesterol or B-lipoproteins, triglycerides or low-density lipoproteins, or decreased high-density lipoproteins (HDL) levels. The investigation was conducted in two stages. At the first stage the indicators of diagnostic value, predictive value and likelihood ratio of changes in laboratory parameters were figured out (first step of the first stage of research). Laboratory syndromes and their constellations (second step), and simultaneous manifestation of a number of laboratory syndromes (third step), which exposed statistically significant differences, or had a significant direct stochastic relationship with the certain bone lesion were identified. The most informative of them, which were confirmed by both statistical criteria at the same time, were selected and therafter, during the second stage, the post-test probability of DBMD manifestations in case of their presence or absence was calculated and represented by the nomogram of Bayes’ theorem. Results. At the first stage were identified markers of bone lesions that have higher sensitivity, negative predictive value, likelihood ratio of negative result, which could be of interest for excluding DBMD, or those that have higher specificity, positive predictive value, likelihood ratio of positive result, which could confirm the diagnosis. During the first step the most characteristic laboratory blood parameters encompassing bone lesions were documented : for both types of DBMD – highly sensitive and most valuable decrease in HDL and highly specific increase in thymol test; only for osteopenia – highly specific increase in total cholesterol; only for osteoporosis – highly sensitive increase in aspartate aminotransferase, increase in gamma globulins and decrease in prothrombin index, moderately sensitive and most valuable increase in AP, and highly specific decrease in potassium. At the second step were estimated constellations of laboratory syndromes as follows : for both types of DBMD – highly specific constellation of cytolysis, mesenchymal-inflammatory syndrome and dyslipidemia, that can be combined with hepatocellular insufficiency, or/and cholestasis; moderate-specific constellation mesenchymal-inflammatory syndrome and dyslipidemia, that can be combined with hepatocellular insufficiency; for osteopenia only – moderate-specific constellation of cytolysis, hepatocellular insufficiency and dyslipidemia; for osteoporosis only – cytolysis or its constellation with hepatocellular insufficiency, that can be combined by cholestasis. At the third step it were revealed highly specific simultaneous manifestation of two different laboratory syndromes out of six characteristic of osteopenia, and highly specific and most valuable simultaneous manifestation of five out of six laboratory syndromes characteristic of osteoporosis. The results obtained during the second stage of our investigation concerned the post-test probability of DBMD manifestations in the absence of a decreased HDL level in patient with LC indicate the possibility of its use in order to exclude any DBMD manifestation. The post-test probability of osteoporosis in the absence of increased LP values is more valuable for excluding osteoporosis in patients with LC, and the maximum value of post-test probability of osteoporosis in a patient with simultaneous manifestation of five studied laboratory syndromes out of six is the most valuable for osteoporosis confirmation. Conclusions. Changes in the laboratory blood parameters of some laboratory syndromes and their constellations have been identified, which are of certain diagnostic value, predictable value and likelihood ratio, since can either confirm or deny the disorders of bone mineral density. 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Materials and methods. 90 patients with LC (27 women, 30.0 %), 63 men (70.0 %),18–66 years of age were randomly examined and stratified for bone lesions according to the T-score in accordance with WHO recommendations. 72 (80.0 %) patients combining LC with DBMD formed a research group (RG), out of which: 46 (63.9 %) patients combined LC with osteopenia (RG-A); 26 (36.1 %) patients combined LC with osteoporosis (RG-B). 18 (20.0 %) patients with LC without DBMD formed a comparison group (CG). 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At the first stage were identified markers of bone lesions that have higher sensitivity, negative predictive value, likelihood ratio of negative result, which could be of interest for excluding DBMD, or those that have higher specificity, positive predictive value, likelihood ratio of positive result, which could confirm the diagnosis. During the first step the most characteristic laboratory blood parameters encompassing bone lesions were documented : for both types of DBMD – highly sensitive and most valuable decrease in HDL and highly specific increase in thymol test; only for osteopenia – highly specific increase in total cholesterol; only for osteoporosis – highly sensitive increase in aspartate aminotransferase, increase in gamma globulins and decrease in prothrombin index, moderately sensitive and most valuable increase in AP, and highly specific decrease in potassium. 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The results obtained during the second stage of our investigation concerned the post-test probability of DBMD manifestations in the absence of a decreased HDL level in patient with LC indicate the possibility of its use in order to exclude any DBMD manifestation. The post-test probability of osteoporosis in the absence of increased LP values is more valuable for excluding osteoporosis in patients with LC, and the maximum value of post-test probability of osteoporosis in a patient with simultaneous manifestation of five studied laboratory syndromes out of six is the most valuable for osteoporosis confirmation. Conclusions. Changes in the laboratory blood parameters of some laboratory syndromes and their constellations have been identified, which are of certain diagnostic value, predictable value and likelihood ratio, since can either confirm or deny the disorders of bone mineral density. 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引用次数: 0

摘要

介绍。一些实验室血液参数的变化,它们指定的实验室综合征及其星座需要研究它们对临床医生识别或排除肝硬化(LC)患者骨矿物质密度(DBMD)紊乱的价值。研究的目的。探讨肝硬化合并骨密度紊乱患者实验室证候及其星座相关参数变化的诊断价值、预测价值及似然比。材料和方法。90例LC患者(女性27例,30.0%),男性63例(70.0%),年龄18-66岁,随机检查,并根据WHO推荐的t评分进行骨病变分层。72例LC合并DBMD患者(80.0%)组成研究组(RG),其中LC合并骨质减少患者(RG- a) 46例(63.9%);LC合并骨质疏松症(RG-B) 26例(36.1%)。无DBMD的LC患者18例(20.0%)为对照组(CG)。实验室综合征的诊断是根据实验室血液参数的异常检测,即:细胞溶解-在血浆中天冬氨酸转氨酶或丙氨酸转氨酶水平升高的情况下;间充质炎症综合征-胸腺酚试验或γ -球蛋白升高;肝细胞功能不全-减少纤维蛋白原或凝血酶原指数,或总蛋白,或白蛋白;胆汁淤积-增加碱性磷酸酶(AP),或γ -谷氨酰转肽酶或总胆红素;门静脉系统分流——钠或钾降低,或肌酐指数升高;血脂异常——胆固醇或b脂蛋白、甘油三酯或低密度脂蛋白升高,或高密度脂蛋白(HDL)水平降低。调查分两个阶段进行。第一阶段计算诊断价值、预测值和实验室参数变化似然比指标(第一阶段研究的第一步)。鉴别出具有统计学差异或与某一骨骼病变有显著直接随机关系的实验室证候及其星座(第二步),以及同时表现的多个实验室证候(第三步)。选择其中信息量最大的,同时被两个统计标准确认的,然后在第二阶段,计算DBMD存在或不存在时的测试后概率,并用贝叶斯定理的nomogram表示。结果。在第一阶段,识别出具有较高敏感性、阴性预测值、阴性结果似然比的骨病变标志物,可用于排除DBMD;或具有较高特异性、阳性预测值、阳性结果似然比的骨病变标志物,可用于确诊。在第一步中,记录了最具特征的实验室血液参数,包括骨病变:对于两种类型的DBMD -高度敏感和最有价值的HDL降低和高度特异性的百里酚测试增加;仅用于骨质减少-总胆固醇高度特异性增加;仅对骨质疏松症-高度敏感的天冬氨酸转氨酶升高,γ球蛋白升高和凝血酶原指数降低,中度敏感和最有价值的AP升高,高度特异性的钾降低。在第二步中,对实验室综合征的分类进行了如下估计:对于两种类型的DBMD -高度特异性的细胞溶解,间质炎症综合征和血脂异常综合征,可合并肝细胞功能不全或/和胆汁淤积;可合并肝细胞功能不全的中度特异性星座间质炎症综合征和血脂异常;仅用于骨质减少-中度特异性细胞溶解,肝细胞功能不全和血脂异常;仅对骨质疏松症-细胞溶解或合并肝细胞功能不全,可合并胆汁淤积。第三步发现了骨质减少症6种不同实验室证候中的2种具有高度特异性的同时表现,骨质疏松症6种实验室证候中的5种具有高度特异性和最有价值的同时表现。在我们调查的第二阶段获得的结果涉及LC患者在没有降低HDL水平的情况下DBMD表现的测试后概率,表明其用于排除任何DBMD表现的可能性。 在LP值未升高的情况下,检测后骨质疏松的概率对于排除LC患者的骨质疏松更有价值,而在6个研究的实验室综合征中同时出现5个的患者中,检测后骨质疏松概率的最大值对于骨质疏松的确认最有价值。结论。已发现一些实验室证候及其星座的实验室血液参数变化,可证实或否认骨密度紊乱,具有一定的诊断价值、可预测价值和似然比。最相关的是:高密度脂蛋白的高度敏感性下降——排除两种类型的骨矿物质密度紊乱;碱性磷酸酶中度敏感增高-排除骨质疏松症;肝硬化患者骨质疏松症的高度特异性同时表现为6个实验室综合征中的5个。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Diagnostic Value, Predictive Value and Likelihood Ratio of Changes in Some Parameters of Laboratory Syndromes and Their Constellations in Patients with Liver Cirrhosis with Disorders of Bone Mineral Density
Introduction. Changes in some laboratory blood parameters, the laboratory syndromes they appoint, and their constellations require investigation of their value for clinicians to identify or exclude disorders of bone mineral density (DBMD) in patients with liver cirrhosis (LC). The aim of the study. To investigate diagnostic value, predictive value and likelihood ratio of changes in certain parameters of laboratory syndromes and their constellations in patients with liver cirrhosis with disorders of bone mineral density. Materials and methods. 90 patients with LC (27 women, 30.0 %), 63 men (70.0 %),18–66 years of age were randomly examined and stratified for bone lesions according to the T-score in accordance with WHO recommendations. 72 (80.0 %) patients combining LC with DBMD formed a research group (RG), out of which: 46 (63.9 %) patients combined LC with osteopenia (RG-A); 26 (36.1 %) patients combined LC with osteoporosis (RG-B). 18 (20.0 %) patients with LC without DBMD formed a comparison group (CG). Laboratory syndromes were diagnosed on the basis of abnormalities detection in laboratory blood parameters, namely: cytolysis – in the case of increased levels of aspartate aminotransferase or alanine aminotransferase in blood plasma; mesenchymal-inflammatory syndrome – increased thymol test or gamma-globulins; hepatocellular insufficiency – decreased fibrinogen or prothrombin indeces, or total protein, or albumin; cholestasis – increased alkaline phosphatase (AP), or gamma-glutamyltranspeptidase or total bilirubin; portosystemic shunting – decreased sodium or potassium, or increased creatinine indeces; dyslipidemia – increased cholesterol or B-lipoproteins, triglycerides or low-density lipoproteins, or decreased high-density lipoproteins (HDL) levels. The investigation was conducted in two stages. At the first stage the indicators of diagnostic value, predictive value and likelihood ratio of changes in laboratory parameters were figured out (first step of the first stage of research). Laboratory syndromes and their constellations (second step), and simultaneous manifestation of a number of laboratory syndromes (third step), which exposed statistically significant differences, or had a significant direct stochastic relationship with the certain bone lesion were identified. The most informative of them, which were confirmed by both statistical criteria at the same time, were selected and therafter, during the second stage, the post-test probability of DBMD manifestations in case of their presence or absence was calculated and represented by the nomogram of Bayes’ theorem. Results. At the first stage were identified markers of bone lesions that have higher sensitivity, negative predictive value, likelihood ratio of negative result, which could be of interest for excluding DBMD, or those that have higher specificity, positive predictive value, likelihood ratio of positive result, which could confirm the diagnosis. During the first step the most characteristic laboratory blood parameters encompassing bone lesions were documented : for both types of DBMD – highly sensitive and most valuable decrease in HDL and highly specific increase in thymol test; only for osteopenia – highly specific increase in total cholesterol; only for osteoporosis – highly sensitive increase in aspartate aminotransferase, increase in gamma globulins and decrease in prothrombin index, moderately sensitive and most valuable increase in AP, and highly specific decrease in potassium. At the second step were estimated constellations of laboratory syndromes as follows : for both types of DBMD – highly specific constellation of cytolysis, mesenchymal-inflammatory syndrome and dyslipidemia, that can be combined with hepatocellular insufficiency, or/and cholestasis; moderate-specific constellation mesenchymal-inflammatory syndrome and dyslipidemia, that can be combined with hepatocellular insufficiency; for osteopenia only – moderate-specific constellation of cytolysis, hepatocellular insufficiency and dyslipidemia; for osteoporosis only – cytolysis or its constellation with hepatocellular insufficiency, that can be combined by cholestasis. At the third step it were revealed highly specific simultaneous manifestation of two different laboratory syndromes out of six characteristic of osteopenia, and highly specific and most valuable simultaneous manifestation of five out of six laboratory syndromes characteristic of osteoporosis. The results obtained during the second stage of our investigation concerned the post-test probability of DBMD manifestations in the absence of a decreased HDL level in patient with LC indicate the possibility of its use in order to exclude any DBMD manifestation. The post-test probability of osteoporosis in the absence of increased LP values is more valuable for excluding osteoporosis in patients with LC, and the maximum value of post-test probability of osteoporosis in a patient with simultaneous manifestation of five studied laboratory syndromes out of six is the most valuable for osteoporosis confirmation. Conclusions. Changes in the laboratory blood parameters of some laboratory syndromes and their constellations have been identified, which are of certain diagnostic value, predictable value and likelihood ratio, since can either confirm or deny the disorders of bone mineral density. The most relevant were as follows : the highly sensitive decrease in high-density lipoproteins - to exclude both type disorders of bone mineral density; the moderately sensitive increase in alkaline phosphatase - to exclude osteoporosis; highly specific simultaneous manifestation of five studied laboratory syndromes out of six - to confirm osteoporosis in patients with liver cirrhosis.
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