中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 1
Jan.  2022
Turn off MathJax
Article Contents

Clinical features and autoantibody characteristics of patients with drug-induced liver injury: An analysis of 419 cases

DOI: 10.3969/j.issn.1001-5256.2022.01.023
Research funding:

National Science and Technology Major Project of China (2018ZX10715-005-003-005);

Beijing Municipal Science & Technology Commission (Z151100004015122);

Beijing Hospitals Authority Clinical medicine Development of special funding (XMLX201706);

Beijing Hospitals Authority Clinical medicine Development of special funding (XMLX202127);

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXT28);

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0302);

Beijing Science and Technology Commission (D161100002716002)

  • Received Date: 2021-05-27
  • Accepted Date: 2021-08-09
  • Published Date: 2022-01-20
  •   Objective  To investigate the clinical features and autoantibody characteristics of patients with drug-induced liver injury (DILI).  Methods  A retrospective analysis was performed for the patients with abnormal liver function who were admitted to Beijing Ditan Hospital, Capital Medical University, from September 2014 to September 2018 and were diagnosed with DILI based on RUCAM score, and related data on admission were collected, including baseline liver function, renal function, routine blood test results, five immune indices, autoantibody, and liver biopsy results. The 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 chi-square test was used to compare the detection rate of autoantibody between the patients with different sexes or types of liver injury. A logistic regression analysis was used to investigate whether autoantibody had a regression relationship with sex, age, and type of injury, and an ordinal logistic regression analysis was performed with baseline laboratory results as independent variables and anti-nuclear antibody (ANA) titer as the dependent variable.  Results  A total of 419 patients with DILI were enrolled in the study, with a median age of 47 (35-55) years, among whom male patients accounted for 32.5% (136/419) and female patients accounted for 67.5% (283/419). Among these 419 patients, 88 (21.5%) had hepatocellular-type liver injury, 87 (21.2%) had mixed-type liver injury, and 235 (57.3%) had cholestasis-type liver injury. The detection rate of autoantibodies was 50.6% (212/419), and the detection rate of ANA was 42.9% (180/419), with a titer of mainly 1∶ 100 (104/180). There was no significant difference in the detection rate of autoantibodies between the patients with different sexes (χ2=2.658, P=0.103) or different types of injury (χ2=0.859, P=0.651). The binary logistic regression analysis showed that autoantibody did not have a regression relationship with sex, age, and type of injury (all P > 0.05) There were significant differences in prothrombin time activity (PTA) and international normalized ratio (INR) between the positive autoantibody group and the negative autoantibody group (t=2.161, P=0.031; Z=-3.010, P=0.003). The ordinal logistic regression analysis showed that INR (odds ratio [OR]=3.101, P=0.040) and IgG (OR=1.043, P=0.014) were associated with ANA grade.  Conclusion  There is a relatively high detection rate of autoantibodies in patients with DILI, and the detection rate of autoantibodies is not associated with sex, age, or type of injury. There are differences in PTA and INR between autoantibody-positive patients and autoantibody-negative patients, and the levels of INR and IgG are correlated with antibody titer.

     

  • loading
  • [1]
    SHEN T, LIU Y, SHANG J, et al. Incidence and etiology of drug-induced liver injury in mainland China[J]. Gastroenterology, 2019, 156(8): 2230-2241. e11. DOI: 10.1053/j.gastro.2019.02.002.
    [2]
    ANDRADE RJ, CHALASANI N, BJÖRNSSON ES, et al. Drug-induced liver injury[J]. Nat Rev Dis Primers, 2019, 5(1): 58. DOI: 10.1038/s41572-019-0105-0.
    [3]
    KE L, LU C, SHEN R, et al. Knowledge mapping of drug-induced liver injury: A scientometric investigation (2010—2019)[J]. Front Pharmacol, 2020, 11: 842. DOI: 10.3389/fphar.2020.00842.
    [4]
    YU YC, MAO YM, CHEN CW, et al. CSH guidelines for the diagnosis and treatment of drug-induced liver injury[J]. Hepatol Int, 2017, 11(3): 221-241. DOI: 10.1007/s12072-017-9793-2.
    [5]
    CHALASANI N, FONTANA RJ, BONKOVSKY HL, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States[J]. Gastroenterology, 2008, 135(6): 1924-1934, 1934. e1-4. DOI: 10.1053/j.gastro.2008.09.011.
    [6]
    FONTANA RJ. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives[J]. Gastroenterology, 2014, 146(4): 914-928. DOI: 10.1053/j.gastro.2013.12.032.
    [7]
    YOKOI T, ODA S. Models of idiosyncratic drug-induced liver injury[J]. Annu Rev Pharmacol Toxicol, 2021, 61: 247-268. DOI: 10.1146/annurev-pharmtox-030220-015007.
    [8]
    STRAVITZ RT, LEE WM. Acute liver failure[J]. Lancet, 2019, 394(10201): 869-881. DOI: 10.1016/S0140-6736(19)31894-X.
    [9]
    CHEN QQ, LU HH, SUN FF, et al. Analysis on chronic factors of patients with drug-induced liver injury[J/CD]. Chin J Liver Dis(Electronic Version), 2020, 12(1): 68-75. DOI: 10.3969/j.issn.1674-7380.2020.01.012.

    陈琦琪, 陆慧慧, 孙芳芳, 等. 药物性肝损伤慢性化相关因素分析[J/CD]. 中国肝脏病杂志(电子版), 2020, 12(1): 68-75. DOI: 10.3969/j.issn.1674-7380.2020.01.012.
    [10]
    HASSAN A, FONTANA RJ. The diagnosis and management of idiosyncratic drug-induced liver injury[J]. Liver Int, 2019, 39(1): 31-41. DOI: 10.1111/liv.13931.
    [11]
    MADDUKURI VC, BONKOVSKY HL. Herbal and dietary supplement hepatotoxicity[J]. Clin Liver Dis (Hoboken), 2014, 4(1): 1-3. DOI: 10.1002/cld.364.
    [12]
    CHOW HC, SO TH, CHOI H, et al. Literature review of traditional Chinese medicine herbs-induced liver injury from an oncological perspective with RUCAM[J]. Integr Cancer Ther, 2019, 18: 1534735419869479. DOI: 10.1177/1534735419869479.
    [13]
    MANNS MP, LOHSE AW, VERGANI D. Autoimmune hepatitis—Update 2015[J]. J Hepatol, 2015, 62(1 Suppl): S100-S111. DOI: 10.1016/j.jhep.2015.03.005.
    [14]
    CHRISTEN U, HINTERMANN E. Pathogens and autoimmune hepatitis[J]. Clin Exp Immunol, 2019, 195(1): 35-51. DOI: 10.1111/cei.13203.
    [15]
    LIU X, DENG GY, YANG SF, et al. Microorganism infection and autoimmune diseases[J]. Chin J Immunol, 2020, 36(17): 2169-2173, the cover 4. DOI: 10.3969/j.issn.1000-484X.2020.17.025.

    刘欣, 邓国英, 杨淑凤, 等. 病原微生物感染与自身免疫病[J]. 中国免疫学杂志, 2020, 36(17): 2169-2173, 封4. DOI: 10.3969/j.issn.1000-484X.2020.17.025.
    [16]
    Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Consensus on the diagnosis and management of autoimmune hepatitis(2015)[J]. J Clin Hepatol, 2016, 32(1): 9-22. DOI: 10.3969/j.issn.1001-5256.2016.01.002.

    中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 自身免疫性肝炎诊断和治疗共识(2015)[J]. 临床肝胆病杂志, 2016, 32(1): 9-22. DOI: 10.3969/j.issn.1001-5256.2016.01.002.
    [17]
    SEBODE M, SCHULZ L, LOHSE AW. "Autoimmune(-Like)" drug and herb induced liver Injury: New insights into molecular pathogenesis[J]. Int J Mol Sci, 2017, 18(9): 1954. DOI: 10.3390/ijms18091954.
    [18]
    WEBER S, BENESIC A, BUCHHOLTZ ML, et al. Antimitochondrial rather than antinuclear antibodies correlate with severe drug-induced liver injury[J]. Dig Dis, 2021, 39(3): 275-282. DOI: 10.1159/000511635.
    [19]
    ALVAREZ F, BERG PA, BIANCHI FB, et al. International Autoimmune Hepatitis Group Report: Review of criteria for diagnosis of autoimmune hepatitis[J]. J Hepatol, 1999, 31(5): 929-938. DOI: 10.1016/s0168-8278(99)80297-9.
    [20]
    WEBER S, BENESIC A, ROTTER I, et al. Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug-induced liver injury from autoimmune hepatitis[J]. Liver Int, 2019, 39(10): 1906-1917. DOI: 10.1111/liv.14195.
    [21]
    HISAMOCHI A, KAGE M, IDE T, et al. An analysis of drug-induced liver injury, which showed histological findings similar to autoimmune hepatitis[J]. J Gastroenterol, 2016, 51(6): 597-607. DOI: 10.1007/s00535-015-1131-7.
    [22]
    DEVARBHAVI H, SINGH R, PATIL M, et al. Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury[J]. J Gastroenterol Hepatol, 2013, 28(1): 161-167. DOI: 10.1111/j.1440-1746.2012.07279.x.
    [23]
    STEPHENS C, ROBLES-DIAZ M, MEDINA-CALIZ I, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry[J]. J Hepatol, 2021, 75(1): 86-97. DOI: 10.1016/j.jhep.2021.01.029.
    [24]
    NORMAN BH. Drug Induced Liver Injury (DILI). Mechanisms and medicinal chemistry avoidance/mitigation strategies[J]. J Med Chem, 2020, 63(20): 11397-11419. DOI: 10.1021/acs.jmedchem.0c00524.
    [25]
    LUCENA MI, SANABRIA J, GARCÍA-CORTES M, et al. Drug-induced liver injury in older people[J]. Lancet Gastroenterol Hepatol, 2020, 5(9): 862-874. DOI: 10.1016/S2468-1253(20)30006-6.
    [26]
    SUTTI S, TACKE F. Liver inflammation and regeneration in drug-induced liver injury: Sex matters![J]. Clin Sci (Lond), 2018, 132(5): 609-613. DOI: 10.1042/CS20171313.
    [27]
    CIRULLI ET, NICOLETTI P, ABRAMSON K, et al. A missense variant in PTPN22 is a risk factor for drug-Induced liver injury[J]. Gastroenterology, 2019, 156(6): 1707-1716. e2. DOI: 10.1053/j.gastro.2019.01.034.
    [28]
    WILLIAMS DP, LAZIC SE, FOSTER AJ, et al. Predicting drug-induced liver injury with bayesian machine learning[J]. Chem Res Toxicol, 2020, 33(1): 239-248. DOI: 10.1021/acs.chemrestox.9b00264.
    [29]
    LIU A, WALTER M, WRIGHT P, et al. Prediction and mechanistic analysis of drug-induced liver injury (DILI) based on chemical structure[J]. Biol Direct, 2021, 16(1): 6. DOI: 10.1186/s13062-020-00285-0.
    [30]
    CHEN Z, MENG X, ZOU L, et al. A dual-emissive phosphorescent polymeric probe for exploring drug-induced liver injury via imaging of peroxynitrite elevation in vivo[J]. ACS Appl Mater Interfaces, 2020, 12(11): 12383-12394. DOI: 10.1021/acsami.9b18135.
  • 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

    Figures(1)  / Tables(5)

    Article Metrics

    Article views (794) PDF downloads(86) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return