中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 10
Oct.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(10): 2369-2375

Clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors

DOI: 10.3969/j.issn.1001-5256.2021.10.022
  • 1.

    Department of Infectious Diseases, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China

  • 2.

    National Clinical Research Center for Infectious Diseases, Fourth Department of Liver Diseases, Medical Center for Liver Diseases, The Second Affiliated Hospital of Southern University of Science and Technology & Shenzhen Third People's Hospital, Shenzhen, Guangdong 518100, China

Research funding:

The Construction of Key Medical Disciplines in Shenzhen and the Sanming Project of Medicine in Shenzhen (SZSM201612014)

  • Received Date: 2021-03-01
  • Accepted Date: 2021-04-06
  • Published Date: 2021-10-20
    Abstract
  •   Objective  To investigate the clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors.  Methods  A total of 129 patients who were diagnosed with liver injury induced by anti-tuberculosis drugs in Shenzhen Third People's Hospital from January 2017 to December 2018 were enrolled and divided into abnormal liver function group with 51 patients (39.53%) and drug-induced liver injury (DILI) group with 78 patients (60.47%), and among these 129 patients, 13 (10.08%) had liver failure. A retrospective analysis was performed for their laboratory markers as well as treatment and prognosis data. The chi-square test was used for comparison of categorical data between two groups; the independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariable logistic regression model was used to investigate the risk factors for DILI and liver failure.  Results  There were significant differences between the DILI group and the abnormal liver function group in chronic HBV co-infection (χ2=5.616, P=0.018), asymptomatic liver injury (χ2=9.451, P=0.002), liver failure (χ2=9.453, P=0.002), need to adjust anti-tuberculosis regimen (χ2=16.787, P < 0.001), time to identification of liver injury (Z=-4.001, P < 0.001), time to liver function recovery (Z=-1.735, P < 0.001), and hepatic encephalopathy (χ2=4.114, P=0.043). The multivariate logistic regression analysis showed that time to identification of liver injury > 8 weeks (odds ratio [OR]=3.94, 95% confidence interval [CI]: 1.02-15.25, P=0.047) and asymptomatic liver injury (OR=7.64, 95% CI: 1.63-35.86, P=0.010) were independent risk factors for DILI; chronic HBV co-infection (OR=14.42, 95% CI: 2.66-78.09, P=0.002) and time to identification of liver injury > 8 weeks (OR=11.97, 95% CI: 2.03-70.50, P=0.006) were independent risk factors for liver failure, while albumin ≥35 g/L (OR=0.07, 95% CI: 0.01-0.51, P=0.010) was a protective factor.  Conclusion  Anti-tuberculosis drugs may induce severe liver injury, and HBV co-infection, asymptomatic liver injury, long time to identification of liver injury, and low albumin level may increase the risk of severe liver injury. Regular follow-up, liver function monitoring, appropriate nutritional support, and HBV screening are important for reducing the risk of liver injury during anti-tuberculosis therapy.

     

    • FullText(HTML)
  • loading
    • References(31)
  • [1]
    WHO. Global tuberculosis report 2020[R/OL]. https://www.who.int/tb/publications/global_report/en/(2020-10-14).
    [2]
    Tuberculosis Society of Chinese Medical Association. Guidelines for anti-tuberculosis drug-induced liver injury[J]. Chin J Tuberc Respir Dis, 2019, 42(5): 343-356. DOI: 10.3760/cma.j.issn.1001-0939.2019.05.007.

    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)[J]. 中华结核和呼吸杂志, 2019, 42(5): 343-356. DOI: 10.3760/cma.j.issn.1001-0939.2019.05.007.
    [3]
    SHEN T, LIU Y, SHANG J, et al. Incidence and etiology of drug induced liver injury in mainland China[J]. Gastroenterology, 2019, 156: 2230-2241. DOI: 10.1053/j.gastro.2019.02.002.
    [4]
    SHARMA SK, BALAMURUGAN A, SAHA PK, et al. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment[J]. Am J Respir Crit Care Med, 2002, 166(7): 916-919. DOI: 10.1164/rccm.2108091.
    [5]
    van HEST R, BAARS H, KIK S, et al. Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment[J]. Clin Infect Dis, 2004, 39(4): 488-496. DOI: 10.1086/422645.
    [6]
    SHARIFZADEH M, RASOULINEJAD M, VALIPOUR F, et al. Evaluation of patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity during antituberculosis[correction of antituberclosis] treatment[J]. Pharmacol Res, 2005, 51(4): 353-358. DOI: 10.1016/j.phrs.2004.10.009.
    [7]
    SAUKKONEN JJ, COHN DL, JASMER RM, et al. An official ATS statement: Hepatotoxicity of antituberculosis therapy[J]. Am J Respir Crit Care Med, 2006, 174(8): 935-952. DOI: 10.1164/rccm.200510-1666ST.
    [8]
    WU YH, WU QH. Literature analysis of 1 949 cases liver injury induced by anti-TB drugs[J]. Northwest Pharm J, 2015, 30(6): 750-753. DOI: 10.3969/j.issn.1004-2407.2015.06.028.

    吴玉华, 武谦虎. 抗结核药致肝损害1949例文献分析[J]. 西北药学杂志, 2015, 30(6): 750-753. DOI: 10.3969/j.issn.1004-2407.2015.06.028.
    [9]
    ZHANG T, DU J, YIN X, et al. Adverse events in treating smear-positive tuberculosis patients in China[J]. Int J Environ Res Public Health, 2015, 13(1): 86. DOI: 10.3390/ijerph13010086.
    [10]
    GE QP, WANG QF, DUAN HF. Clinical analysis of protionamide and para-aminosalicylic acid induced hepatotoxicity in 129 cases[J]. Chin J Tuberc Respir Dis, 2013, 36(10): 737-740. DOI: 10.3760/cma.j.issn.1001-0939.2013.10.008.

    戈启萍, 王庆枫, 段鸿飞. 含丙硫异烟胺和对氨基水杨酸治疗方案发生药物性肝损伤129例临床分析[J]. 中华结核和呼吸杂志, 2013, 36(10): 737-740. DOI: 10.3760/cma.j.issn.1001-0939.2013.10.008.
    [11]
    ZHANG MY, LEI JP, YAN SM, et al. Liver injury induced by anti-tuberculosis drugs and anti-tuberculosis therapy for patients with liver disease: Introduction of the experience of diagnosis and treatment in Chinese mainland and "Taiwan Guidelines for TB Diagnosis & Treatment"[J]. J Clin Hepatol, 2015, 31(11): 1776-1781. DOI: 10.3969/j.issn.1001-5256.2015.11.004.

    张明媛, 雷建平, 闫世明, 等. 抗结核药物所致肝损伤及肝病患者抗结核药物治疗——大陆地区诊治建议与台湾《结核病诊治指引》相关介绍[J]. 临床肝胆病志, 2015, 31(11): 1776-1781. DOI: 10.3969/j.issn.1001-5256.2015.11.004.
    [12]
    YU YC, MAO YM, CHEN CW. Guidelines for the management of drug-induced liver injury[J]. J Pract Hepatol, 2017, 20(2): 257-274. DOI: 10.3969/j.issn.1672-5069.2017.02.039.

    于乐成, 茅益民, 陈成伟. 药物性肝损伤诊治指南[J]. 实用肝脏病杂志, 2017, 20(2): 257-274. DOI: 10.3969/j.issn.1672-5069.2017.02.039.
    [13]
    AITHAL GP, WATKINS PB, ANDRADE RJ, et al. Case definition and phenotype standardization in drug-induced liver injury[J]. Clin Pharmacol Ther, 2011, 89(6): 806-815. DOI: 10.1038/clpt.2011.58.
    [14]
    JIN XL, YANG ZB, ZHAN SH, et al. Influencing factor of liver dysfunction of inpatients of tuberculosis with initial treatment[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2020, 14(5): 394-400.

    金小琳, 杨智彬, 詹淑华, 等. 1501例初治住院结核病患者肝功能异常的影响因素[J/CD]. 中华实验和临床感染病杂志(电子版), 2020, 14(5): 394-400.
    [15]
    LI HL, WEN DD, BEI CL, et al. Analysis of anti-tuberculosis drug induced liver injury and its drug use cost in the hospital before and after the special rectification[J]. Chin J Clin Pharmacol Ther, 2019, 24(9): 1030-1036. DOI: 10.12092/j.issn.1009-2501.2019.09.011.

    李红丽, 文丹丹, 贝承丽, 等. 专项整治前后结核患者肝损伤及药物使用费用对比分析[J]. 中国临床药理学与治疗学, 2019, 24(9): 1030-1036. DOI: 10.12092/j.issn.1009-2501.2019.09.011.
    [16]
    LEE AM, MENNONE JZ, JONES RC, et al. Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: Experience from three public health tuberculosis clinics[J]. Int J Tuberc Lung Dis, 2002, 6(11): 995-1000.
    [17]
    NOOREDINVAND HA, CONNELL DW, ASGHEDDI M, et al. Viral hepatitis prevalence in patients with active and latent tuberculosis[J]. World J Gastroenterol, 2015, 21(29): 8920-8926. DOI: 10.3748/wjg.v21.i29.8920.
    [18]
    KIM WS, LEE SS, LEE CM, et al. Hepatitis C and not hepatitis B virus is a risk factor for anti-tuberculosis drug induced liver injury[J]. BMC Infect Dis, 2016, 16: 50. DOI: 10.1186/s12879-016-1344-2.
    [19]
    LIU YM, CHENG YJ, LI YL, et al. Antituberculosis treatment and hepatotoxicity in patients with chronic viral hepatitis[J]. Lung, 2014, 192(1): 205-210. DOI: 10.1007/s00408-013-9535-8.
    [20]
    KANEKO Y, NAGAYAMA N, KAWABE Y, et al. Drug-induced hepatotoxicity caused by anti-tuberculosis drugs in tuberculosis patients complicated with chronic hepatitis[J]. Kekkaku, 2008, 83(1): 13-19. http://europepmc.org/abstract/MED/18283910
    [21]
    WANG NT, HUANG YS, LIN MH, et al. Chronic hepatitis B infection and risk of antituberculosis drug-induced liver injury: Systematic review and meta-analysis[J]. J Chin Med Assoc, 2016, 79(7): 368-374. DOI: 10.1016/j.jcma.2015.12.006.
    [22]
    CHEN L, BAO D, GU L, et al. Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment[J]. BMC Infect Dis, 2018, 18(1): 295. DOI: 10.1186/s12879-018-3192-8.
    [23]
    ZHENG J, GUO MH, PENG HW, et al. The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: A meta-analysis of cohort studies[J]. Epidemiol Infect, 2020, 148: e290. DOI: 10.1017/S0950268820002861.
    [24]
    ZHU CH, ZHAO MZ, CHEN G, et al. Baseline HBV load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis[J]. J Huazhong Univ Sci Technolog Med Sci, 2017, 37(1): 105-109. DOI: 10.1007/s11596-017-1702-3.
    [25]
    CHENG SQ. Diagnosis and treatment of coinfection of pulmonary tuberculosis and chronic hepatitis B[J]. World Chin J Dig, 2016, 24(18): 2785-2798. DOI: 10.11569/wcjd.v24.i18.2785.

    程书权. 应重视乙型肝炎合并肺结核的临床诊断与治疗[J]. 世界华人消化杂志, 2016, 24(18): 2785-2798. DOI: 10.11569/wcjd.v24.i18.2785.
    [26]
    TWEED CD, WILLS GH, CROOK AM, et al. Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study[J]. BMC Med, 2018, 16(1): 46. DOI: 10.1186/s12916-018-1033-7.
    [27]
    MASINI EO, MANSOUR O, SPEER CE, et al. Using survival analysis to identify risk factors for treatment interruption among new and retreatment tuberculosis patients in Kenya[J]. PLoS One, 2016, 11(10): e0164172. DOI: 10.1371/journal.pone.0164172.
    [28]
    TELEMAN MD, CHEE CB, EARNEST A, et al. Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore[J]. Int J Tuberc Lung Dis, 2002, 6(8): 699-705. http://old.med.wanfangdata.com.cn/viewHTMLEn/PeriodicalPaper_JJ029828197.aspx
    [29]
    SUN HY, CHEN IL, GAU CS, et al. A prospective study of hepatitis during antituberculous treatment in taiwanese patients and a review of the literature[J]. J Formos Med Assoc, 2009, 108(2): 102-111. DOI: 10.1016/s0929-6646(09)60040-1.
    [30]
    LEE CM, LEE SS, LEE JM, et al. Early monitoring for detection of antituberculous drug-induced hepatotoxicity[J]. Korean J Intern Med, 2016, 31(1): 65-72. DOI: 10.3904/kjim.2016.31.1.65.
    [31]
    PATTERSON B, ABBARA A, COLLIN S, et al. Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests[J]. J Infect, 2021, 82(2): 240-244. DOI: 10.1016/j.jinf.2020.09.038.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (565) PDF downloads(66) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return