中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 4
Apr.  2019
Turn off MathJax
Article Contents

Recent advances in drug-induced liver injury: Potential mechanisms, pathological features, and biomarkers

DOI: 10.3969/j.issn.1001-5256.2019.04.049
Research funding:

 

  • Published Date: 2019-04-20
  • Drug-induced liver injury ( DILI) is one of the main causes of acute liver failure, black box warnings, and drug withdrawal from the market, and it is also a major concern in public health, drug research and development, and the pharmaceutical industry. However, a lack of specific diagnostic markers for DILI makes the diagnosis of this disease a major challenge for clinicians. This article summarizes the recent advances in DILI research, including potential mechanisms, pathological features, biomarkers, and in vitro methods, in order to provide a reference for clinical and pathological diagnosis and prognostic evaluation of DILI.

     

  • loading
  • [1]SGRO C, CLINARD F, OUAZIR K, et al.Incidence of druginduced hepatic injuries:A French populationbased study[J].Hepatology, 2002, 36 (2) :451-455.
    [2]BJORNSSON ES, BERGMANN OM, BJORNSSON HK, et al.Incidence, presentation, and outcomes in patients with druginduced liver injury in the general population of Iceland[J].Gastroenterology, 2013, 144 (7) :1419-1425.
    [3]KIM KA.Current status of liver diseases in Korea:Toxic and alcoholic liver diseases[J].Korean J Hepatol, 2009, 15 (6) :s29-s33.
    [4]de ABAJO FJ, MONTERO D, MADURGA M, et al.Acute and clinically relevant drug-induced liver injury:A population based case-control study[J].Br J Clin Pharmacol, 2004, 58 (1) :71-80.
    [5]RUIGO'MEZ A, BRAUER R, RODRI'GUEZ LA, et al.Ascertainment of acute liver injury in two European primary care databases[J].Eur J Clin Pharmacol, 2014, 70 (10) :1227-1235.
    [6]ORTEGAALONSO A, ANDRADE RJ.Chronic liver injury induced by drugs and toxins[J].J Dig Dis, 2018, 19 (9) :514-521.
    [7]HILLMAN L, GOTTFRIED M, WHITSETT M, et al.Clinical features and outcomes of complementary and alternative medicine induced acute liver failure and injury[J].Am J Gastroenterol, 2016, 111 (7) :958-965.
    [8]SINGH D, CHO WC, UPADHYAY G.Drug-induced liver toxicity and prevention by herbal antioxidants:An overview[J].Front Physiol, 2016, 6:363.
    [9]WATKINS PB, KAPLOWITZ N, SLATTERY JT, et al.Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily:A randomized controlled trial[J].JA-MA, 2006, 296 (1) :87-93.
    [10]KULLAKUBLICK GA, ANDRADE RJ, MERZ M, et al.Druginduced liver injury:Recent advances in diagnosis and risk assessment[J].Gut, 2017, 66 (6) :1154-1164.
    [11]KIM SH, NAISBITT DJ.Update on advances in research on idiosyncratic drug-induced liver injury[J].Allergy Asthma Immunol Res, 2016, 8 (1) :3-11.
    [12]CORSINI A, BORTOLINI M.Drug-induced liver injury:The role of drug metabolism and transport[J].J Clin Pharmacol, 2013, 53 (5) :463-474.
    [13]ROTH AD, LEE MY.Idiosyncratic drug-induced liver injury (IDILI) :Potential mechanisms and predictive assays[J].Biomed Res Int, 2017, 2017 (1) :1-23.
    [14]UTKARSH D, LORETZ C, LI AP.In vitro evaluation of hepatotoxic drugs in human hepatocytes from multiple donors:Identification of P450 activity as a potential risk factor for drug-induced liver injuries[J].Chem Biol Interact, 2016, 255:12-22.
    [15]TAN XQ, YANG GQ, ZHANG L, et al.Research progress on CYP2E1 mediating toxicity by exogenous chemicals[J].China Occup Med, 2016, 43 (2) :234-236. (in Chinese) 谭孝琼, 杨光谦, 张林, 等.细胞色素P450 2E1介导外源性化合物毒性损伤研究进展[J].中国职业医学, 2016, 43 (2) :234-236.
    [16]MACKAY RJ, MCENTYRE CJ, HENDERSON C, et al.Trimethylaminuria:Causes and diagnosis of a socially distressing condition[J].Clin Biochem Rev, 2011, 32 (1) :33-34.
    [17]MARQUES SC, IKEDIOBI ON.The clinical application of UGT1A1pharmacogenetic testing:Gene-environment interactions[J].Hum Genomics, 2010, 4 (4) :238-249.
    [18]CRETTOL S, PETROVIC N, MURRAY M.Pharmacogenetics of phase I and phase II drug metabolism[J].Curr Pharm Des, 2010, 16 (2) :204-219.
    [19]KALIYAPERUMAL K, GROVE JI, DELAHAY RM, et al.Pharmacogenomics of drug-induced liver injury (DILI) :Molecular biology to clinical applications[J].J Hepatol, 2018, 69 (4) :948-957.
    [20]GMEZLECHN MJ, TOLOSA L, DONATO MT.Metabolic activation and drug-induced liver injury:In vitro approaches for the safety risk assessment of new drugs[J].J Appl Toxicol, 2016, 36 (6) :752-768.
    [21]BHARATHI V, RENGARAJAN RL, RADHAKRISHNAN R, et al.Effects of a medicinal plant Macrotyloma uniflorum, (Lam.) Verdc.formulation (MUF) on obesity-associated oxidative stress-induced liver injury[J].Saudi J Biol Sci, 2018, 25 (6) :1115-1121.
    [22]AYALA A, MUOZ MF, ARGELLES S.Lipid peroxidation:Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal[J].Oxid Med Cell Longev, 2014, 2014 (6) :1-31.
    [23]SHEHU AI, MA X, VENKATARAMANAN R.Mechanisms of drug-induced hepatotoxicity[J].Clin Liver Dis, 2017, 21 (1) :35-54.
    [24]MASUBUCHI Y, SUDA C, HORIE T.Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice[J].J Hepatol, 2005, 42 (1) :110-116.
    [25]ALEO MD, LUO Y, SWISS R, et al.Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump[J].Hepatology, 2014, 60 (3) :1015-1022.
    [26]MOSEDALE M, WATKINS PB.Drug-induced liver injury:Advances in mechanistic understanding that will inform risk management[J].Clin Pharmacol Ther, 2017, 101 (4) :469-480.
    [27]DARA L, LIU ZX, KAPLOWITZ N.Mechanisms of adaptation and progression in idiosyncratic drug induced liver injury, clinical implications[J].Liver Int, 2016, 36 (2) :158-165.
    [28]KLEINER DE, CHALASANI NP, LEE WM, et al.Hepatic histological findings in suspected drug-induced liver injury:Systematic evaluation and clinical associations[J].Hepatology, 2014, 59 (2) :661-670.
    [29]KLEINER DE.The histopathological evaluation of drug-induced liver injury[J].Histopathology, 2017, 70 (1) :81-93.
    [30]YANG RY, ZHAO XY.Significance of liver histopathological examination in diagnosis and treatment of drug-induced liver injury[J].J Clin Hepatol, 2018, 34 (6) :1172-1175. (in Chinese) 杨瑞园, 赵新颜.肝组织病理学检查在药物性肝损伤诊治中的意义[J].临床肝胆病杂志, 2018, 34 (6) :1172-1175.
    [31]KHOURY T, RMEILEH AA, YOSHA L, et al.Drug induced liver injury:Review with a focus on genetic factors, tissue diagnosis, and treatment options[J].J Clin Transl Hepatol, 2015, 3 (2) :99-108.
    [32]LAWAL A, ZHANG M, DITTMAR M, et al.Heme oxygenase-1protects endothelial cells from the toxicity of air pollutant chemicals[J].Toxicol Appl Pharmacol, 2015, 284 (3) :281-291.
    [33]BAKHAUTDIN B, DAS D, MANDAL P, et al.Protective role of HO-1 and carbon monoxide in ethanol-induced hepatocyte cell death and liver injury in mice[J].J Hepatol, 2014, 61 (5) :1029-1037.
    [34]GAO Y, CAO Z, YANG X, et al.Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury[J].Proteomics Clin Appl, 2017, 11 (1-2) .
    [35]CHURCH RJ, KULLAK-UBLICK GA, AUBRECHT J, et al.Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury:An international collaborative effort[J].Hepatology, 2019, 69 (2) :760-773.
    [36]ROBLES-DAZ M, MEDINA-CALIZ I, STEPHENS C, et al.Biomarkers in DILI:One more step forward[J].Front Pharmacol, 2016, 7:267.
    [37]LIU XQ, WU WX, GENG XC, et al.Research progress of biomarkers of druginduced liver injury[J].Chin J New Drugs, 2018, 27 (1) :47-52. (in Chinese) 刘小茜, 吴文晓, 耿兴超, 等.药物性肝损伤生物标志物研究进展[J].中国新药杂志, 2018, 27 (1) :47-52.
    [38]CHO YE, SONG BJ, AKBAR M, et al.Extracellular vesicles as potential biomarkers for alcohol-and drug-induced liver injury and their therapeutic applications[J].Pharmacol Ther, 2018, 187:180-194.
    [39]BENESIC A, ROTTER I, DRAGOI D, et al.Development and validation of a test to identify drugs that cause idiosyncratic drug-induced liver injury[J].Clin Gastroenterol Hepatol, 2018, 16 (9) :1488-1494.e5.
  • 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

    Article Metrics

    Article views (1244) PDF downloads(328) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return