肝硬化隐匿型肝性脑病常用诊断方法的比较研究

发布时间：2018-07-23 17:47

【摘要】：背景肝性脑病(hepatic encephalopathy,HE)是肝硬化患者一种主要的、尚未被解决的并发症。轻微型肝性脑病(minimal hepatic encephalopathy,MHE)或隐匿型肝性脑病(covert hepatic encephalopathy,CHE)可增加患者的死亡率和住院风险,健康相关生命质量(Health Related Quality of Life,HRQo L)受损及看护者的负担增加。检测MHE或CHE可以指导治疗,可能改善临床结局和生命质量。然而,临床实践中对肝硬化患者实施MHE或CHE的检测并不常见。HE早期诊断和治疗的主要障碍是缺乏一个有效的、标准化的检测及描述HE的方法。缺乏客观和灵敏的HE分级方法,限制了我们对于HE流行病学和发病机制的理解和评估HE靶向治疗疗效的困难。因此,近期的AASLD/EASL指南推荐:使用2种或更多种辅助检测方法诊断隐匿型肝性脑病。这些方法包括纸笔测试,如肝性脑病心理学评分(psychometric hepatic encephalopathy score,PHES);神经生理学测试,如临界闪烁频率(critical flicker frequency,CFF);计算机测试,如Encephal App Stroop。简易智能量表(mini-mental state examination,MMSE)是一种最普遍使用的评估认知精神状况的方法,其在认知障碍筛查中具有良好的信度和效度。过去不仅被应用于肝病的研究,在国外一些研究中,甚至用于评估肝性脑病的严重性和作为肝性脑病的监测方法之一。然而,我国研究人员尚未进行类似方面的研究。目的本研究采用近期欧美肝病协会肝性脑病共识指南推荐的诊断标准,即使用2种或以上方法诊断隐匿型肝性脑病。在此基础上,初步探索简易智能量表(MMSE)、临界闪烁频率(CFF)、肝性脑病心理学评分(PHES)和斯特鲁普测试(Encephal App Stroop)等隐匿型肝性脑病(CHE)常用检测方法的临床应用价值。方法纳入110例肝硬化失代偿期患者和81例无肝病的对照者,以PHES-4分作为CHE的参考阈值,分析得出CFF和Stroop测验的测试时间诊断CHE的阈值。以PHES、CFF、Stroop测验中至少2项阳性作为诊断CHE的“金标准”,评价这3种检测方法诊断CHE的临床应用价值。同时将简易智能量表根据测试的功能不同划分为多个项目,分别分析各子项目对于肝性脑病的初筛及预测价值。统计学方法采用t检验、单因素方差分析及ROC曲线分析。结果110例肝硬化患者中,肝硬化无肝性脑病(HE0)患者40例,CHE 52例,肝性脑病II级18例。(1)对照组CFF值和Stroop测验的总时间分别为(43.70±1.92)Hz、(201.17±20.65)s,HE0组CFF值为(41.40±1.85)Hz,高于CHE组的(38.33±2.32)Hz,差异有统计学意义(t=-7.116,P0.01);HE0组Stroop测验的总时间为(197.91±26.68)s,短于CHE组的(253.24±33.33)s,差异有统计学意义(t=8.936,P0.01)。(2)当以PHES-4分作为CHE的参考阈值时,CFF诊断CHE的阈值为39Hz,敏感度为94.9%,特异度为73.1%,AUC值为0.879;Stroop测验的总时间诊断CHE的阈值为233.80s,敏感度为83.3%,特异度为71.7%,AUC值为0.803。(3)CHE组患者PHES5项子测试中的NCT-A、NCT-B和DST的完成时间分别为(80.27±36.05)、(124.18±55.96)和(25.03±8.23)s,与HE0组的(56.68±18.82)、(80.00±25.58)和(34.68±8.75)s相比,差异均有统计学意义(t=3.691、4.108、-4.780,P值均0.01);与PHES和Stroop测验联合诊断HE0、CHE和HE2的检测结果比较,以CFF值39Hz作为检测阈值的一致率分别达95.0%、61.5%和100.0%。(4)肝功能Chi ld-pugh评分与MMSE总分、时间定向、空间定向、注意力和计算力、回忆、写句子、画五角形7个项目的Pearson相关系数分别为-0.352,-0.417,-0.342,-0.243,-0.275,-0.303,-0.278,P值均0.01);HE0、CHE和OHE 3组患者间MMSE总分差异显著(P值均0.001),尤其OHE患者的MMSE总分均值相比CHE患者及HE0患者明显减低,分别为18.50±4.17分、24.93±4.23分、27.88±2.70分。HE0与CHE两组间比较时发现,时间定向和空间定向2个项目均无统计学差异(P0.05),而OHE组不论与HE0组或CHE组比较,时间定向和空间定向均差异显著(P均0.001)。结论PHES中的NCT-A、NCT-B和DST3个子测试检测CHE的效能较高。CFF和Stroop测验也是较为可靠的筛选鉴别CHE的检测方法,具有客观和特异性强的检测优势。MMSE总分、时间定向和空间定向3个项目对于OHE具有一定的预测价值,而CHE的诊断仍需结合多种诊断方法,提高筛查率。
[Abstract]:Background hepatic encephalopathy (hepatic encephalopathy, HE) is a major, yet not resolved complication in patients with cirrhosis. Mild hepatic encephalopathy (minimal hepatic encephalopathy, MHE) or occult hepatic encephalopathy (covert hepatic encephalopathy, CHE) can increase the mortality and risk of hospitalization, and the health related quality of life (Health) Elated Quality of Life, HRQo L) damage and the burden of caregivers increase. Detection of MHE or CHE can guide treatment, may improve clinical outcome and quality of life. However, in clinical practice, the detection of MHE or CHE for patients with cirrhosis is not a common obstacle to the early diagnosis and treatment of.HE is the lack of an effective, standardized test and The lack of an objective and sensitive method of HE classification limits our understanding of the epidemiology and pathogenesis of HE and the difficulty of assessing the efficacy of HE targeting therapy. Therefore, the recent AASLD/EASL guidelines recommend 2 or more auxiliary detection methods for the diagnosis of occult hepatic encephalopathy. These include the paper pen test, such as the liver. Psychometric hepatic encephalopathy score (PHES); neurophysiological tests, such as the critical scintillation frequency (critical flicker frequency, CFF); computer testing, such as Encephal App Stroop. simple intelligence scale, is the most commonly used party to assess cognitive mental status. It has good reliability and validity in the screening of cognitive impairment. In the past, it was not only used in the study of liver disease, but also in some foreign studies, and even used to assess the severity of hepatic encephalopathy and one of the monitoring methods of hepatic encephalopathy. However, the researchers in our country have not done a similar study. The diagnostic criteria recommended by the European and American Liver Association liver encephalopathy consensus guidelines are to use 2 or more methods to diagnose occult hepatic encephalopathy. On this basis, we preliminarily explore the simple Intelligence Scale (MMSE), critical scintillation frequency (CFF), hepatic encephalopathy psychological score (PHES) and Stroop test (Encephal App Stroop) and other occult hepatic encephalopathy (CH). E) the clinical value of common detection methods. Methods included in 110 patients with decompensated cirrhosis and 81 cases of non liver disease control, using PHES-4 score as the reference threshold of CHE, the threshold of the test time of CFF and Stroop test was analyzed. At least 2 positive of the PHES, CFF, Stroop test were used as the "gold standard" for diagnosing CHE. The value of these 3 methods was used to diagnose the clinical application of CHE. At the same time, the simple intelligent scale was divided into multiple items according to the function of the test. The initial screening and prediction value of each sub item for hepatic encephalopathy was analyzed. The statistical method was t test, single factor analysis of variance and ROC curve analysis. Results of 110 cases of liver cirrhosis, liver 40 cases of sclerotic hepatic encephalopathy (HE0), 52 cases of CHE and 18 cases of hepatic encephalopathy II. (1) the total time of CFF value and Stroop test in the control group was (43.70 + 1.92) Hz, (201.17 + 20.65) s, and HE0 group CFF value was (41.40 + 1.85) Hz, higher than that of CHE group (38.33 + 2.32) Hz, the difference was statistically significant (197., 197.). 91 + 26.68) s, shorter than group CHE (253.24 + 33.33) s, the difference was statistically significant (t=8.936, P0.01). (2) when PHES-4 score was used as the reference threshold for CHE, CFF diagnostic CHE threshold was 39Hz, sensitivity was 94.9%, specificity was 73.1%, AUC value was 0.879; the total time diagnostic threshold of Stroop test was 83.3%, specificity was 71.7%, The AUC value was NCT-A in the PHES5 subtest of group 0.803. (3) CHE, the completion time of NCT-B and DST was (80.27 + 36.05), (124.18 + 55.96) and (25.03 + 8.23) s, compared with the HE0 group (56.68 + 18.82), (80 + 25.03) and (34.68 + 8.75) s. Compared with the detection results of HE0, CHE and HE2, the consistent rate of CFF value 39Hz as detection threshold was 95%, 61.5% and 100.0%. (4) Chi ld-pugh score and MMSE total score, time orientation, spatial orientation, attention and computing power, memory, sentence writing, and five corners of 7 items were -0.352, -0.417, etc. 243, -0.275, -0.303, -0.278, and P were all 0.01). The total score of MMSE total score in HE0, CHE and OHE 3 groups was significantly different (P value 0.001), especially the MMSE total value of OHE patients was significantly lower than that of CHE patients and patients, respectively 18.50 + 4.17, 24.93 + 4.23, 27.88 + 2.70 and two groups. Time orientation and spatial orientation 2 items were found. There were no statistical differences (P0.05), but in group OHE, both time orientation and spatial orientation were significantly different from HE0 group or CHE group (P 0.001). Conclusion NCT-A, NCT-B and DST3 sub tests in PHES were more effective and more reliable for detection of CHE, which was more objective and specific. 3 items of.MMSE total score, time orientation and spatial orientation have a certain predictive value for OHE, and the diagnosis of CHE still needs to be combined with a variety of diagnostic methods to improve the screening rate.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575.2;R747.9

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