药物性肝损伤临床风险信号发现:挑战与进展

景婧; 何婷婷; 王睿林; 张帆; 牛明; 郭玉明; 朱云; 肖小河; 王伽伯

doi:10.3969/j.issn.1001-5256.2020.03.002

药物性肝损伤临床风险信号发现:挑战与进展

DOI: 10.3969/j.issn.1001-5256.2020.03.002

1. 解放军总医院第五医学中心中西医结合诊疗与研究中心
2. 湖南中医药大学第一中医临床学院
3. 解放军总医院第五医学中心全军中医药研究所

基金项目:

国家自然科学基金重点项目(81630100);国家自然科学基金创新群体项目(81721002)；国家“重大新药创制”科技重大专项课题(2015ZX09501-004-001-008)；国家公益性行业专项课题(201507004-04)；国家自然科学基金资助项目(81673806)；军委后勤保障部卫生局应用基础研究项目(17BJZ53)；

详细信息

中图分类号: R575
计量
- 文章访问数: 375
- HTML全文浏览量: 18
- PDF下载量: 331
- 被引次数: 0
出版历程
- 出版日期: 2020-03-20

Detection of the risk signals of drug-induced liver injury: Challenges and advances

Treatment and Research Center of Integration of Traditional and Western Medicine, The Fifth Medical Center of Chinese PLA General Hospital

Research funding:

摘要

摘要: 早期发现药物性肝损伤(DILI)临床风险信号,并对其进行有效监测,对临床上DILI预防和管理极为重要。但是,由于当前DILI临床风险信号还存在灵敏度不足、专属性不强等问题,为风险信号的发现与监测带来了巨大挑战,同时也给建立DILI风险防控对策带来了难题。分析了DILI临床风险信号发现所面临的挑战,梳理了基于临床常用指标的风险信号对DILI早期识别、预测和预警的适用性和局限性,提出基于特异生物标志物的DILI临床风险信号发现与监测模式,并阐述其潜在的临床应用价值,以期为针对性制定DILI风险防控对策提供科学参考。
- 药物性肝损伤 /
- 生物学标记 /
- 诊断 /
- 预后 /
- 疾病易感性
Abstract: Early detection and effective monitoring of the risk signals of drug-induced liver injury( DILI) are of great importance in the prevention and management of DILI in clinical practice. However,the lack of high sensitivity and strong specificity in the detection of risk signals brings great challenges to the identification and monitoring of risk signals and causes difficulties in establishing the strategies for the prevention and control of DILI. This article analyzes the challenges in the identification of DILI risk signals,summarizes the applicability and limitations of risk signals based on commonly used indices in early recognition,prediction,and early warning of DILI,proposes an identification and monitoring model for DILI risk signals based on specific biomarkers,and elaborates on their potential clinical values,so as to provide a scientific basis for developing targeted strategies for the prevention and control of the risk of DILI.
- drug-induced liver injury /
- biological markers /
- diagnosis /
- prognosis /
- disease susceptibility

HTML全文

参考文献(40)

[1] 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.

[2] XIAO XH,TANG JY,MAO YM,et al. Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury[J]. Acta Pharm Sin B,2019,9(3):648-658.

[3] ZHOU Y,YANG L,LIAO Z,et al. Epidemiology of drug-induced liver injury in China:A systematic analysis of the Chinese literature including 21,789 patients[J]. Eur J Gastroenterol Hepatol,2013,25(7):825-829.

[4] 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.

[5] CHEN M,SUZUKI A,BORLAK J,et al. Drug-induced liver injury:Interactions between drug properties and host factors[J]. J Hepatol,2015,63(2):503-514.

[6] HOOFNAGLE JH,BJÖRNSSON ES. Drug-induced liver injury-Type and phenotypes[J]. N Engl J Med,2019,381(3):264-273.

[7] STINE JG,CHALASANI N. Chronic liver injury induced by drugs:A systematic review[J]. Liver Int,2015,35(11):2343-2353.

[8] European Association for the Study of the Liver. EASL clinical practice guidelines:Drug-induced liver injury[J]. J Hepatol,2019,70(6):1222-1261.

[9] KWO PY,COHEN SM,LIM JK. ACG clinical guideline:Evaluation of abnormal liver chemistries[J]. Am J Gastroenterol,2017,112(1):18-35.

[10] U. S. Department of Health and Human Services FDA,Center for Drug Evaluation and Research(CDER),Center for Biologics Evaluation and Research(CBER). Guidance for Industry.Drug-Induced Liver Injury:Premarketing Clinical Evaluation[EB/OL].(2009). https://www. fda. gov/downloads/Guidances/UCM174090. pdf.

[11] Chinese Medical Association of Chinese Society for Tuberculosis. Guidelines for the diagnosis and treatment of antituberculotic drug-induced liver injury[J]. Chin J Tuberc Respir Dis,2019,42(5):343-356.(in Chinese)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.

[12] CHALASANI N,BONKOVSKY HL,FONTANA R,et al. Features and outcomes of 899 patients with drug-induced liver injury:The DILIN prospective study[J]. Gastroenterology,2015,148(7):1340-1352. e7.

[13] FONTANA RJ,HAYASHI PH,GU J,et al. Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset[J]. Gastroenterology,2014,147(1):96-108. e4.

[14] JEONG R,LEE YS,SOHN C,et al. Model for end-stage liver disease score as a predictor of short-term outcome in patients with drug-induced liver injury[J]. Scand J Gastroenterol,2015,50(4):439-446.

[15] ROBLES-DIAZ M,LUCENA MI,KAPLOWITZ N,et al. Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury[J]. Gastroenterology,2014,147(1):109-118. e5.

[16] MEDINA-CALIZ I,ROBLES-DIAZ M,GARCIA-MUÑOZ B,et al. Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury[J]. J Hepatol,2016,65(3):532-542.

[17] ZHU Y,NIU M,CHEN J,et al. Hepatobiliary and pancreatic:Comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients[J]. J Gastroenterol Hepatol,2016,31(8):1476-1482.

[18] JING J,WANG R,ZHAO X,et al. Association between the concurrence of pre-existing chronic liver disease and worse prognosis in patients with an herb-Polygonum multiflorum thunb. induced liver injury:A case-control study from a specialised liver disease center in China[J]. BMJ Open,2019.[Epub ahead of print]

[19] LO RS,KRISHNAMOORTHY R,FREEMAN JG,et al. Cholestasis and biliary dilatation associated with chronic ketamine abuse:A case series[J]. Singapore Med J,2011,52(3):e52-e55.

[20] SCHWAB GP,WETSCHER GJ,VOGL W,et al. Methimazole-induced cholestatic liver injury,mimicking sclerosing cholangitis[J]. Langenbecks Arch Chir,1996,381(4):225-227.

[21] HORSLEY-SILVA JL,DOW EN,MENIAS CO,et al. Docetaxel induced sclerosing cholangitis[J]. Dig Dis Sci,2015,60(12):3814-3816.

[22] LIN G,WANG JY,LI N,et al. Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum[J]. J Hepatol,2011,54(4):666-673.

[23] Cooperative Group for Hepatic and Gall Diseases,Chinese Society of Gastroenterology, Chinese Medical Association.Expert consensus on diagnosis and treatment of quinazoline alkaloids-related sinusoidal obstruction syndrome(2017,Nanjing)[J]. J Clin Hepatol,2017,33(9):1627-1637.(in Chinese)中华医学会消化病学分会肝胆疾病协作组．吡咯生物碱相关肝窦阻塞综合征诊断和治疗专家共识意见(2017年，南京)[J]．临床肝胆病杂志，2017,33(9):1627-1637.

[24] STINE JG,NORTHUP PG. Autoimmune-like drug-induced liver injury:A review and update for the clinician[J]. Expert Opin Drug Metab Toxicol,2016,12(11):1291-1301.

[25] 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.

[26] KLEINER DE. Drug-induced Liver Injury:The hepatic pathologist's approach[J]. Gastroenterol Clin North Am,2017,46(2):273-296.

[27] KULLAK-UBLICK GA,ANDRADE RJ,MERZ M,et al. Drug-induced liver injury:Recent advances in diagnosis and risk assessment[J]. Gut,2017,66(6):1154-1164.

[28] CLARKE JI,DEAR JW,ANTOINE DJ. Recent advances in biomarkers and therapeutic interventions for hepatic drug safetyfalse dawn or new horizon?[J]. Expert Opin Drug Saf,2016,15(5):625-634.

[29] LUNDBÄCK P,LEA JD,SOWINSKA A,et al. A novel high mobility group box 1 neutralizing chimeric antibody attenuates drug-induced liver injury and postinjury inflammation in mice[J]. Hepatology,2016,64(5):1699-1710.

[30] DEAR JW,CLARKE JI,FRANCIS B,et al. Risk stratification after paracetamol overdose using mechanistic biomarkers:Results from two prospective cohort studies[J]. Lancet Gastroenterol Hepatol,2018,3(2):104-113.

[31] CHURCH R,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.

[32] ANTOINE DJ,JENKINS RE,DEAR JW,et al. Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity[J]. J Hepatol,2012,56(5):1070-1079.

[33] HUEBENER P,PRADERE JP,HERNANDEZ C,et al. The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification fol owing necrosis[J]. J Clin Invest,2015,125(2):539-550.

[34] ANDERSSON U,LINDBERG J,WANG S,et al. A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran[J]. Biomarkers,2009,14(8):572-586.

[35] LI C,RAO T,CHEN X,et al. HLA-B*35∶01 allele is a potential biomarker for predicting Polygonum multiflorum-induced liver injury in humans[J]. Hepatology,2019,70(1):346-357.

[36] NICOLETTI P,AITHAL GP,BJORNSSON ES,et al. Association of liver injury from specific drugs,or groups of drugs,with polymorphisms in HLA and other genes in a genome-wide association study[J]. Gastroenterology,2017,152(5):1078-1089.

[37] AITHAL GP. Pharmacogenetic testing in idiosyncratic druginduced liver injury:Current role in clinical practice[J]. Liver Int,2015,35(7):1801-1808.

[38] GROVE JI,AITHAL GP. Human leukocyte antigen genetic risk factors of drug-induced liver toxicology[J]. Expert Opin Drug Metab Toxicol,2015,11(3):395-409.

[39] ZHANG L,NIU M,WEI AW,et al. Risk profiling using metabolomic characteristics for susceptible individuals of drug-induced liver injury caused by Polygonum multiflorum[J]. Arch Toxicol,2019.[Epub ahead of print]

[40] WANG JB,ZHU Y,BAI ZF,et al. Guidelines for the diagnosis and management of herb-induced liver injury[J]. Chin J Integr Med,2018,24(9):696-706.

施引文献

资源附件(0)

访问统计