Gene MTB/RIF、TB-IGRA检测与传统组织病理学检查在脊柱结核诊断中的应用价值

Application value of GeneXpert MTB/RIF, TB-IGRA and traditional histopathology in the diagnosis of spinal tuberculosis

中文关键词:  脊柱结核  诊断  组织病理检查  Gene MTB/RIF检测  γ干扰素释放试验

英文关键词:Application value of Gene MTB/RIF, TB-IGRA and traditional histopathology in the diagnosis of spinal tuberculosis

中文摘要:

  【摘要】 目的：评估传统组织病理学（简称“病理”）检查与Gene MTB/RIF（简称“Xpert”）、γ干扰素释放试验（TB-IGRA）在脊柱结核诊断中的应用价值。方法：回顾性分析2017年11月～2020年6月在我院经临床诊断为“脊柱结核”的131例患者资料，男79例，女52例；年龄18～90岁（50±18.0岁）；颈椎7例，胸椎39例，胸腰段11例，腰椎57例，腰骶椎12例，骶椎5例。所有患者术前进行TB-IGRA检测，然后通过穿刺或手术获得病灶组织，分别进行病理检查与Xpert检测。病理检查结果分四类：Ⅰ类为确诊结核、Ⅱ类为倾向于结核，Ⅲ类为疑诊结核，Ⅳ类为未确诊结核。Ⅰ类、Ⅱ类病理结果支持脊柱结核诊断，Ⅲ类、Ⅳ类不支持脊柱结核诊断。计算三者的阳性率与阴性率。以病理检查为参照标准，计算Xpert、TB-IGRA的敏感度、特异度，三者单独检测的阳性率、联合检测的阳性率分别进行比较，计算Kappa值评估两者的一致性，并绘制Xpert、TB-IGRA检测的受试者工作特征（receiver operating characteristic，ROC）曲线并计算曲线下面积（area under curve，AUC），评估Xpert、TB-IGRA检测的价值。结果：所有患者中，病理确诊为结核85例（64.9%，95%CI为56.6%～73.2%），病理未确诊结核46例（35.1%，95%CI为26.8%～43.4%）；Xpert检测阳性79例（60.3%，95%CI为51.0%～68.1%），阴性52例（39.7%，95%CI为31.9%～49%），发现RNA聚合酶β亚基的编码基因（rpoB）突变6例（4.6%，95%CI为0.95%～8.20%）；TB-IGRA检测阳性99例（75.6%，95%CI为68.1%.83.0%），阴性32例（24.4%，95%CI为17.0%～31.9%）。病理检查与Xpert检测联合诊断脊柱结核89例（67.9%，95%CI为59.02%～75.32%），未确诊结核42例（32.1%，95%CI为24.68%～40.98%）。病理检查与TB-IGRA检测联合诊断脊柱结核107例（81.7%，95%CI为74.97%～88.39%），未确诊结核24例（18.3%，95%CI为11.61%～25.03%）。Xpert检测敏感度为87.1%（74/85），特异度为91.3%（42/46）；TB-IGR检测敏感度为90.6%（77/85），特异度为52.2%（24/46）。病理检查与Xpert检测联合诊断脊柱结核的阳性率为67.9%（89/131）；病理检查与TB-IGRA检测联合诊断脊柱结核的阳性率为81.7%（107/131）；三者联合诊断脊柱结核的阳性率为82.4%（108/131）。以临床诊断结果作为参照，TB-IGRA联合病理检查阳性率高于病理检查（χ2=9.435，P=0.002），三者联合检测阳性率高于病理检查（χ2=9.855，P=0.002），也高于Xpert与病理检查联合（χ2=16.681，P＜0.001）。病理检查与Xpert两种检测确诊脊柱结核的Kappa值为0.76（95%CI为0.631～0.873），一致性好；病理检查与TB-IGRA两种检测确诊脊柱结核的Kappa值为0.46（95%CI为0.295～0.616），一致性较好。Xpert检测诊断脊柱结核的AUC为0.892；TB-IGRA检测诊断脊柱结核的AUC为0.751。结论：TB-IGRA检测敏感性较高，Xpert检测特异性较高，并且能发现利福平耐药突变；二者联合病理学检查对诊断脊柱结核具有较高的应用价值。

英文摘要:

  【Abstract】 Objectives: To evaluate the value of traditional histopathology, Gene Xpert MTB/RIF (Xpert) and interferon-gamma release assay for mycobacterium tuberculosis(TB-IGRA) in the diagnosis of spinal tuberculosis. Methods: The data of 131 patients diagnosed as "spinal tuberculosis" in our hospital from November 2017 to June 2020 were analyzed retrospectively. Among the 131 patients, 79(60.3％) were males and 52(39.7％) were females; aged 18 to 90 years (50.0±18.0 years old). The locations of the disease: 39 cases of thoracic vertebrae, 57 cases of lumbar vertebrae, 12 cases of lumbosacral vertebrae, 11 cases of thoracolumbar segment, 7 cases of cervical vertebrae and 5 cases of sacral vertebrae. All patients were tested for TB-IGRA before operation, and then the lesion tissues were obtained by puncture or operation. Histopathological examination and Xpert test were carried out respectively, and the positive and negative rates were calculated. Histopathological diagnosis was divided into four categories: category Ⅰ was confirmed tuberculosis, category Ⅱ was inclined to tuberculosis,category Ⅲ was suspected tuberculosis and category Ⅳ was undiagnosed tuberculosis. Categories Ⅰ and Ⅱ supported the diagnosis of spinal tuberculosis, while Ⅲ and Ⅳ didn′t support. With histopathological diagnosis as the gold standard, the sensitivity and specificity of Xpert and TB-IGRA examination were obtained and the Kappa value was calculated to evaluate their consistency. The positive rates of single detection and combined detection were compared respectively. The receiver operating characteristic(ROC) curve of Xpert and TB-IGRA was drawn and the area under curve(AUC) was calculated to evaluate the value of Xpert and TB-IGRA. Results: Among the 131 patients, 85 were diagnosed with confirmed TB by histopathology(64.9%, 95%CI: 56.6%-73.2%), 46 were undiagnosed TB by histopathology (35.1%, 95%CI: 26.8%-43.4%), Xpert was positive in 79 cases (60.3%, 95%CI: 51.0%-68.1%), and negative in 52 cases(39.7%, 95%CI: 31.9%-49%), rpoB mutations were found in 6 cases(4.6%, 95%CI 0.95%-8.20%), and TB-IGRA was positive in 99 cases(75.6%, 95%CI: 68.1%-83.0%), negative in 32 cases(24.4%, 95%CI 17.0%-31.9%). 89 cases of spinal tuberculosis(67.9%, 95%CI: 59.02%-75.32%) were diagnosed by histopathological examination and Xpert, 42 cases of undiagnosed tuberculosis(32.1%, 95%CI: 24.68%-40.98%). 107 cases of spinal tuberculosis(81.7%, 95%CI 74.97%-88.39%) were diagnosed by histopathological examination and TB-IGRA, 24 cases of undiagnosed tuberculosis (18.3%, 95%CI 11.61%-25.03%). The sensitivity and specificity of Xpert were 87.1% (74/85) and 91.3%(42/46); the sensitivity and specificity of TB-IGRA were 90.6%(77/85) and 52.2%(24/46). The positive rate of histopathology combined with Xpert test in the diagnosis of spinal tuberculosis was 67.9%(89/131); the positive rate of histopathology combined with TB-IGRA test in the diagnosis of spinal tuberculosis was 81.7%(107/131); the positive rate of the three examination combined diagnosis of spinal tuberculosis was 82.4%(108/131). Based on the clinical diagnostic criteria, the positive rate of TB-IGRA combined with pathological examination was higher than that of pathological examination(χ2=9.435, P=0.002), the positive rate of TB-IGRA combined with pathological examination was higher than that of pathological examination(χ2=9.855, P=0.002), and also higher than that of Xpert combined with pathological examination(χ2=16.681, P<0.001). The Kappa value of spinal tuberculosis diagnosed by histopathological examination and Xpert was 0.76(95%CI 0.631-0.873), that of histopathological examination and TB-IGRA was 0.46(95%CI 0.295-0.616). The AUC of spinal tuberculosis diagnosed by Xpert was 0.892, and that of TB-IGRA was 0.751. Conclusions: TB-IGRA has high sensitivity, Xpert has high specificity, and rifampicin resistant mutations can be found; the combined Histopathological examination of them has high application value in the diagnosis of spinal tuberculosis.