Characteristics of Infection Indexes in Patients with Antituberculous Drug-induced Liver Injury
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摘要:
目的 回顾性分析肺结核合并HIV与单纯肺结核患者抗结核药物性肝损伤的感染指标特征,评估临床危险因素及相关性。 方法 收集服用抗结核药物诱导肝损伤的患者,其中肺结核患者55例,肺结核合并HIV感染患者39例。记录临床资料,采集空腹静脉血,流式细胞术检测CD3+、CD4+、CD8+T 细胞比率,ELISA 检测血清降钙素原(procalcitonin, PCT)、白细胞介素-6(interleukin-6, IL-6)、C-反应蛋白(C-reactive protein, CRP)、血清淀粉样蛋白A(serum amyloid A protein, SAA)、红细胞沉降率(erythrocyte sedimentation rate, ESR)。 结果 在年龄、性别构成、身高、体重、体质指数等方面两两比较差异无统计学意义(P > 0.05),免疫功能2组比较CD4+T淋巴细胞及CD4%、CD4/CD8%表达不同,差异具有统计学意义(P < 0.05)。炎症指标中CRP及SAA在单纯肺结核患者中明显升高,差异具有统计学意义(P < 0.05),同时本研究显示在抗结核药物性肝损伤的肺结核组中,SAA与肝损伤严重程度密切相关,差异有统计学意义(P < 0.05)。在肺结核并HIV感染组中,IL-6与肝损伤严重程度密切相关,差异有统计学意义(P < 0.05)。 结论 感染指标在不同类型患者的抗结核药物性肝损伤中表达不同,感染指标SAA与IL-6升高,与不同类型患者的抗结核药物性肝损伤严重程度有关。 Abstract:Objective To retrospectively analyze the characteristics of infection indicators of antituberculosis drug-related liver injury in patients with pulmonary tuberculosis combined with HIV versus those with pulmonary tuberculosis alone, and to assess clinical risk factors and correlations. Methods Patients with liver injury induced by antituberculosis drugs were collected, including 55 cases of pulmonary tuberculosis and 39 cases of pulmonary tuberculosis combined with HIV infection. Clinical data were recorded, fasting venous blood was collected, CD3+, CD4+ and CD8+ T cell ratios were detected by flow cytometry, and serum PCT, IL-6, CRP, SAA and ESR were detected by ELISA. Results There were no significant differences in age, gender composition, height, weight and body mass index between the two groups, and the immune function of the two groups were compared, the expression of CD4+ T lymphocytes and CD4%, CD CD4/CD8% were statistically different (P < 0.05). The levels of CRP and SAA in inflammatory indexes were higher in patients with single pulmonary tuberculosis (P < 0.05), and the degree of liver injury in patients with TB and HIV was lower than in the group of patients with TB alone, suggesting that the diseased population with normal immune function, which has a strong inflammatory response, is one of the risk factors leading to liver injury in the treatment of anti-tuberculosis drugs. Also this study showed that SAA was strongly correlated with the severity of liver injury in the tuberculosis group with anti-tuberculosis drug liver injury and the results were statistically significant (P < 0.05). In the pulmonary TB with HIV infection group, IL-6 was closely associated with the severity of liver injury and the results were statistically significant (P < 0.05). Conclusions Infection indicators are expressed differently in anti-tuberculosis drug liver injury with different types of patients. The increase of SAA and IL-6 is related to the severity of anti-tuberculosis drug liver injury in different types of patients. -
表 1 抗结核药物性肝损伤的单纯肺结核患者与肺结核并HIV患者的一般资料特点(
$\bar x \pm s $ )Table 1. Characteristics of general data of patients with simple TB and patients with TB and HIV with liver injury from anti-TB drugs (
$\bar x \pm s $ )项目 单纯肺结核(n = 55) 肺结核并HIV (n = 39) t/χ2 P 年龄(岁) 42.3 ± 10.5 45.4 ± 12.6 0.951 0.294 性别/(男/女) 30/25 20/19 0.655 0.435 身高(cm) 162.1 ± 8.7 165.2 ± 6.3 0.388 0.674 体重(kg) 61.2 ± 11.2 58.3 ± 9.4 0.771 0.496 体质指数 20.8 ± 2.3 19.4 ± 2.5 0.554 0.398 表 2 抗结核药物性肝损伤的肺结核患者与肺结核并HIV患者外周血T淋巴细胞亚群比较(
$\bar x \pm s $ )Table 2. Comparison of peripheral blood T lymphocyte subsets in TB patients with liver injury from anti-TB drugs and TB and HIV patients (
$\bar x \pm s $ )项目 单纯肺结核(n = 55) 肺结核并HIV (n = 39) t P CD3计数(个) 692 ± 101 489 ± 198 0.765 0.381 CD4计数(个) 432 ± 112 228 ± 138 7.211 0.003* CD8计数(个) 226 ± 98 190 ± 105 0.451 0.512 CD3% 72.1 ± 11.2 61.3 ± 10.4 0.231 0.754 CD4% 36.65 ± 2.23 21.34 ± 7.54 5.965 0.004* CD8% 25.11 ± 1.89 29.87 ± 1.55 0.224 0.816 CD4/CD8% 1.25 ± 0.58 0.56 ± 0.35 4.211 0.005* *P < 0.05。 表 3 抗结核药物性肝损伤的肺结核患者与肺结核并HIV患者CRP、IL-6、PCT、SAA、ESR比较(
$\bar x \pm s $ )Table 3. Comparison of CRP,IL-6,PCT,SSA,ESR in TB patients with liver injury from anti-TB drugs and TB and HIV patients (
$\bar x \pm s $ )项目 单纯肺结核(n = 55) 肺结核并HIV (n = 39) t P CRP(mg/L) 36 ± 12 19 ± 13 5.765 0.003* IL-6(pg/L) 65 ± 25 87 ± 31 0.951 0.213 PCT(ng/L) 3.1 ± 1.4 2.6 ± 0.9 0.231 0.797 SAA(mg/L) 198 ± 36 112 ± 43 6.814 0.002* ESR(mm/h) 42 ± 25 33 ± 21 0.366 0.712 *P < 0.05。 表 4 CRP、IL-6、PCT、SAA、ESR与病情严重程度相关性分析结果(
$\bar x \pm s $ )Table 4. Results of correlation analysis between CRP,IL-6,PCT,SAA,ESR and severity of disease (
$\bar x \pm s $ )项目 CRP(μg/mL) IL-6(pg/mL) PCT(ng/L) SAA(mg/L) ESR(mm/h) 1级(n = 18) 12 ± 7 25 ± 10 0.65 ± 0.11 24 ± 15 16 ± 8 2级(n = 16) 27 ± 11 31 ± 13 1.33 ± 0.55 38 ± 19 20 ± 9 3级(n = 11) 21 ± 11 43 ± 12 2.15 ± 0.76 66 ± 17 30 ± 13 4级(n = 8) 29 ± 11 55 ± 10 3.01 ± 0.91 97 ± 21 39 ± 15 5级(n = 2) 35 ± 15 67 ± 26 3.3 ± 1.21 121 ± 34 44 ± 22 Spearman系数 0.411 0.198 0.248 0.798 0.257 P 0.114 0.462 0.354 0.001* 0.338 注:*P < 0.05。 表 5 CRP、IL-6、PCT、SAA、ESR与病情严重程度相关性分析结果(
$\bar x \pm s $ )Table 5. Results of correlation analysis between CRP,IL-6,PCT,SAA,ESR and severity of disease (
$\bar x \pm s $ )项目 CRP (μg/mL) IL-6 (pg/mL) PCT (ng/L) SAA (mg/L) ESR (mm/h) 1级(n = 13例) 10 ± 6 22 ± 11 0.51 ± 0.12 63 ± 17 9 ± 5 2级(n = 11例) 14 ± 7 38 ± 12 1.21 ± 0.62 98 ± 19 16 ± 7 3级(n = 9例) 16 ± 9 49 ± 15 1.45 ± 0.77 115 ± 21 21 ± 11 4级(n = 5例) 20 ± 10 58 ± 11 2.55 ± 0.83 175 ± 28 26 ± 13 5级(n = 1例) 21 ± 11 68 ± 13 2.61 ± 0.75 192 ± 37 32 ± 16 Spearman系数 0.278 0.921 0.290 0.311 0.166 P 0.297 < 0.001* 0.276 0.241 0.539 注:*P < 0.05。 -
[1] 赵红,范颖,谢雯. 抗结核药物所致肝损伤临床研究进展[J]. 现代医药卫生,2018,34(13):1953-1955. [2] 雷建平,吴雪琼,张文宏. 抗结核药物所致肝损伤相关危险因素及临床处置对策[J]. 中国防痨杂志,2013,35(11):858-865. [3] 中华人民共和国国家卫生和计划生育委员会. 肺结核诊断标准(WS 288—2017)[J]. 新发传染病电子杂志,2018,3(1):59-61. [4] 王月珍,杜普,仲绥生,等. 高效联合抗逆转录病毒疗法结合中医分期辨证治疗HIV/AIDS 29例临床研究[J]. 国际中医中药杂志,2011,33(5):385-388. doi: 10.3760/cma.j.issn.1673-4246.2011.05.001 [5] 中华医学会结核病学分会, 抗结核药物性肝损伤诊治指南(2019年版), 中华结核和呼吸杂志, 2019, 36(10): 343-356. [6] Kullak-Ublick G A,Andrade R J,Merz M,et al. Drug induced liver injury:recent advances in diagnosis and risk assessment[J]. Gut,2017,66(6):1154-1164. doi: 10.1136/gutjnl-2016-313369 [7] 沈银洲,卢洪洲. 艾滋病合并结核病诊治现状[J]. 中国实用内科杂志,2015,35(8):671-674. [8] 周林,陈磊,赖钰基,等. TB/HIV双重感染患者抗结核治疗药品不良反应分析[J]. 中国防痨杂志,2011,33(2):77-81. [9] 中华医学会感染病学分会艾滋病学组,中华医学会热带病与寄生虫学分会艾滋病学组. HIV合并结核分枝杆菌感染诊治专家共识[J]. 中华临床感染病杂志,2017,10(2):81-90. [10] 江颖仪,李德宪,劳穗华,等. 血清淀粉样蛋白A,降钙素原,超敏C反应蛋白检测对肺结核合并肺炎的诊断价值[J]. 南方医科大学学报,2021,41(3):453-458. doi: 10.12122/j.issn.1673-4254.2021.03.20 [11] 吴念宁,陈万,邹俊,等. HIV/TB病人抗结核治疗强化期发生药物性肝炎的研究[J]. 中国艾滋病性病,2014,20(1):13-16. [12] 黄琪淋,温莎,叶绍燕,等. 血清SHBG与SAA4联合检测对涂阴肺结核辅助诊断的价值[J]. 中国感染控制杂志,2019,18(12):1144-1149. doi: 10.12138/j.issn.1671-9638.20195193 [13] 严建新,倪英玲,江天. 中性粒细胞/淋巴细胞比值及感染性指标在肺结核诊断中的应用[J]. 中国卫生检验杂志,2018,28(14):1753-1756. [14] 唐玉珍,陈竹,吴蓓,等. 169例急性药物性肝损害的临床特征及易感因素分析[J]. 中国肝脏病杂志(电子版),2014,6(2):31-34. doi: 10.3969/j.issn.1674-7380.2014.02.008