HIV感染并发结核性脑膜炎患者的临床特征及其预后影响因素分析

Analysis on clinical characteristics and prognostic of human immunodeficiency virus infected patients with tuberculous meningitis

目的分析HIV感染并发结核性脑膜炎(TBM)患者的临床特征、短期预后及其影响因素。方法回顾性分析2017年1月1日至12月31日于成都市公共卫生临床医疗中心诊断为TBM的148例患者,将52例HIV感染并发TBM者作为观察组,96例未并发HIV感染者作为对照组。比较两组患者的临床表现、脑脊液检查、头颅影像学及临床转归等方面的差异。结果观察组发生营养不良和贫血者分别占78.8%(41/52)和51.9%(27/52),并发其他肺外结核者占73.1%(38/52),均高于对照组[分别占39.6%(38/96)、30.2%(29/96)、30.2%(29/96)],差异均有统计学意义(χ^2值分别为20.89、6.76、8.27,P值均<0.05)。观察组脑脊液压力、白细胞总数、蛋白含量、葡萄糖和氯化物水平中位数(四分位数)分别为185.0(141.0,225.0)mm H2O(1mm H2O=0.0098kPa)、30.0(4.0,175.0)×10^6/L、1141.2(762.8,1548.6)mg/L、2.3(1.7,2.7)mmol/L、117.0(111.1,121.9)mmol/L,对照组分别为284.0(197.5,315.0)mm H2O、360.0(280.0,415.0)×10^6/L、1660.0(1270.0,1900.0)mg/L、1.4(1.2,1.8)mmol/L、105.1(102.6,112.4)mmol/L,差异均有统计学意义(Z值分别为3.63、4.79、2.57、4.17、4.19,P值均<0.05)。头颅影像学检查显示,观察组脑组织梗死灶发生率为46.2%(24/52),明显高于对照组的28.1%(27/96),差异有统计学意义(χ^2=4.85,P=0.028)。观察组病情好转者有20例(38.5%),恶化及死亡者有32例(61.5%);对照组好转者有62例(64.6%),恶化及死亡者有34例(35.4%);两组比较差异有统计学意义(χ^2=9.32,P<0.05)。观察组病情恶化及死亡者中体质量指数(BMI)<18.0、重度贫血(血红蛋白<60g/L)、CD4 +T淋巴细胞计数<50 个/μl、规范抗结核及抗病毒治疗者分别占56.3%(18/32)、43.8%(14/32)、53.1%(17/32)、28.1%(9/32)和40.6%(13/32),与病情好转者的25.0%(5/20)、15.0%(3/20)、20.0%(4/20)、60.0%(12/20)和75.0%(15/20)相比,差异均有统计学意义(χ^2值分别为4.87、4.62、5.61、5.19、5.85,P值均<0.05)。多因素logistic回归分析显示,CD4 +T淋巴细胞计数<50个/μl [OR(95%CI)=4.21(1.15~15.45)]是患者预后的危险因素,规范抗结核治疗[OR(95%CI)=0.28(0.05~0.94)]及规范抗病毒治疗[OR(95%CI)=0.13(0.04~0.47)]是患者预后的保护因素。结论 HIV感染对TBM患者的临床表现、脑脊液指标、头颅影像学检查和预后均有明显影响,及时进行规范的抗结核及抗病毒治疗有助于改善患者预后。

Objective To analyze the clinical characteristics, short-term prognosis and influencing factors of patients with human immunodeficiency virus (HIV) infection complicated with tuberculous meningitis (TBM).Methods One hundred and forty-eight cases of TBM patients were retrospectively collected from Chengdu Public Health Clinical Medical Center between January 2017 and December 2017. Among them, 52 were infected with HIV (HIV+/TBM group) and 96 were not infected with HIV (HIV-/TBM group). The clinical manifestations, cerebrospinal fluid (CSF) examination results, skull imaging and clinical outcomes of the patients in the two groups were compared.Results The incidences of malnutrition, anemia, and complication with other extrapulmonary tuberculosis in the HIV+/TBM group were 78.8%(41/52), 51.9%(27/52), and 73.1%(38/52), respectively, which were higher than those in the HIV-/TBM group (39.6%(38/96), 30.2%(29/96), and 30.2%(29/96)), and the differences were statistically significant (χ^ 2 values were 20.89, 6.76, and 8.27;P values were <0.05). The median (quartile) of CSF pressure, white cell count, protein content, sugar and chloride levels were 185.0 (141.0, 225.0) mm H2O (1mm H2O=0.0098 kPa), 30.0 (4.0, 175.0)×10^ 6/L, 1141.2 (762.8, 1548.6) mg/L, 2.3 (1.7, 2.7) mmol/L, and 117.0 (111.1, 121.9) mmol/L in the HIV+/TBM group and 284.0 (197.5, 315.0) mm H2O, 360.0 (280.0, 415.0)×10^ 6/L, 1660.0 (1270.0, 1900.0) mg/L, 1.4 (1.2, 1.8) mmol/L, and 105.1 (102.6, 112.4) mmol/L in the HIV-/TBM group;the differences were statistically significant (Z values were 3.63, 4.79, 2.57, 4.17, and 4.19;P values were <0.05). The incidence of cerebral infarction was 46.2%(24/52) in the HIV+/TBM group and 28.1%(27/96) in the HIV-/TBM group;the difference was statistically significant (χ^ 2=4.85, P=0.028). In the HIV+/TBM group, 20 cases (38.5%) improved and 32 cases (61.5%) deteriorated or died at discharge, and in the HIV-/TBM group, 62 cases (64.6%) improved and 34 cases (35.4%) deteriorated or died, showing significant difference (χ^2=9.32, P<0.05). In the HIV+/TBM group, among the patients who deteriorated or died, patients with BMI<18,severe anemia (hemoglobin <60g/L), CD4 +T lymphocyte count <50/μl, standard anti-tuberculosis treatment and standard antiviral treatment accounted for 56.3%(18/32), 43.8%(14/32), 53.1%(17/32), 28.1%(9/32), and 40.6%(13/32), respectively, and those among patients who improved accounted for 25.0%(5/20), 15.0%(3/20), 20.0%(4/20), 60.0%(12/20), and 75.0%(15/20), showing significant differences (χ^ 2=4.87, 4.62, 5.61, 5.19, and 5.85, respectively, all P<0.05). Multivariate logistic regression analysis showed that CD4 +T lymphocyte count <50/μl (OR(95%CI)=4.21(1.15-15.45)) was risk factor, whereas receiving standard anti-tuberculosis (OR(95%CI)=0.28(0.05-0.94)) and standard antiviral therapy (OR(95%CI)=0.13(0.04-0.47)) were protective factor for the prognosis of patients. Conclusion HIV infected TBM patients are more likely to have altered clinical manifestations, CSF indexes, cranial imaging and prognosis. Timely initiation of standardized anti-tuberculous treatment and anti-viral therapy could improve the prognosis of patients.