朱晗瑀　李金凤　张咪　王雪　吴冬雪　孙淑丰　冯福民

摘要 目的 通过检测抗结核药物性肝损伤（ADLI）患者中GRP78的定量表达，分析血清因子GRP78诊断ADLI的能力，为解决“ADLI 的发生要依靠临床指标加经验丰富的临床医生来共同判定”这一临床困境，提供更多理论依据。方法 以唐山市第四医院2016 年 7—12 月期间肺结核患者为研究对象，将有肝损伤患者63例作为病例组，按照成组匹配原则，选择同时期63例非肝损伤患者为对照组，酶联免疫吸附测定（ELISA）法检测GRP78的表达。SPSS23.0进行统计分析，检验水准α为0.05。结果 病例组和对照组之间在年龄、性别、体质量指数（BMI）、吸烟、饮酒、文化程度方面差异均无统计学意义（P>0.05）。而病例组血清因子的含量明显高于对照组（P<0.05）。GRP78曲线下面積为0.83，诊断的临界值为1.17（ng/mL），诊断结果与临床诊断具有中度一致性（Kappa=0.50），灵敏度和特异度分别为74.60%和79.37%。结论 GRP78对ADLI患者具有一定的诊断能力，但效果一般。

关键词 抗结核药物性肝损伤;GRP78;结核病

中图分类号  R965    文献标识码  A    文章编号  1671-0223（2020）10-085-03

EVALUATION OF THE DIAGNOSTIC EFFECT OF SERUM FACTOR GRP78 IN ANTI-TUBERCULOSIS DRUG-INDUCED LIVER INJURY Zhu Hanyu，Li Jinfeng，Zhang Mi，et al. School of Public Health， North China University of Science and Technology， Tangshan 063210， China

Abstract  Objective To detect the quantitative expression of GRP78 in patients with ADLI and analyze the ability of serum factor GRP78 to diagnose ADLI， in order to solve the clinical dilemma of "the occurrence of ADLI depends on clinical indicators and experienced clinicians to jointly determine"， provide more theoretical basis. Methods Taking the pulmonary tuberculosis patients in the Fourth Hospital of Tangshan City from July to December 2016 as the research object，63 patients with liver injury as a case group.According to group matching principle，63 cases of non liver injury in the same period were selected as the control group.Detect the expression of GRP78 by ELISA.SPSS23.0 for statistical analysis，the test level α is 0.05.Results There was no significant difference in age，gender，BMI，smoking，drinking and education between the case group and the control group （P>0.05）.The content of serum factor in case group was significantly higher than in control group （P<0.05）.The area under GRP78 curve was 0.83.The critical value of diagnosis was 1.17 （ng/mL），and the diagnostic results were in moderate agreement with clinical diagnosis （Kappa=0.50），The sensitivity and specificity were 74.60% and 79.37%， respectively.Conclusion GRP78 has a certain diagnostic ability for ADLI patients， but the effect is not so good.

Key words  ADLI; GRP78; Tuberculosis

在过去几十年里，人类与结核病的战争未曾间断，并在预防和控制结核疾病方面取得了巨大的成就。但是，目前我国仍是全球30个结核病高负担国家之一，每年新发结核病患者约90万例，位居全球第3位[1]，要实现“消灭结核”的终极目标仍需要进一步的努力。长期持续联合化疗是保证结核病治疗效果的唯一措施。但是，在4种一线抗结核药物中，异烟肼（INH）、利福平（RFP）和吡嗪酰胺（PZA）均有不同程度的肝细胞毒性，治疗结核病过程中经常伴随着肝损伤的发生[2]，从而使标准化疗方案的实施受到限制。而肝损伤的发生往往会伴随着肝细胞的过度凋亡，细胞凋亡主要由死亡受体途径、线粒体途径和内质网应激途径3条通路共同介导。其中……