药物性肝损伤的研究进展

杨雪; 涂荣芳; 杨晋辉

doi:10.3969/j.issn.1001-5256.2020.03.006

药物性肝损伤的研究进展

DOI: 10.3969/j.issn.1001-5256.2020.03.006

昆明医科大学第二附属医院消化内科

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中图分类号: R575
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出版历程
- 出版日期: 2020-03-20

Research advances in drug-induced liver injury

Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University

摘要

摘要: 药物性肝损伤(DILI)发病机制复杂、个体差异较明显。DILI发生早期诊治预后较好,但由于DILI无明显的特殊临床症状,多不能于早期发现,当错过最佳治疗时间后,可能进展为不可逆的肝衰竭,病死率升高,且晚期DILI除肝移植外并无有效的治疗方法。因此,对DILI患者早期做出诊断、治疗至关重要。总结了近年来DILI的相关进展,包括可疑药物、危险因素、发病机制、病理特点、临床分型和表现、诊断标准及评估、网络数据库研究等,以期为DILI的早期诊断、临床分型、指导治疗、判断预后等提供依据。
- 药物性肝损伤 /
- 病理状态,体征和症状 /
- 危险因素 /
- 诊断
Abstract: Drug-induced liver injury( DILI) has a complex pathogenesis and obvious individual difference. Early diagnosis and treatment of DILI may achieve good prognosis,but due to a lack of specific clinical symptoms,most cases cannot be identified in the early stage. If no timely treatment is given,DILI may progress to irreversible liver failure with a high mortality rate,and there are no effective therapies for advanced DILI except liver transplantation. Therefore,early diagnosis and treatment are of great importance for patients with DILI. This article summarizes the recent research advances in DILI,including suspected drugs,risk factors,pathogenesis,pathological features,clinical types and manifestations,diagnostic criteria and evaluation,and network database,in order to provide a basis for early diagnosis,clinical typing,treatment guidance,and prognostic evaluation of DILI.
- drug-induced liver injury /
- pathological conditions,signs and symptoms /
- risk factors /
- diagnosis

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参考文献(42)

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

[2] CHURCH RJ,WAT KINS PB. Serum biomarkers of drug-induced liver injury:Current status and future directions[J]. J Dig Dis,2018,20(1):2-10.

[3] REUBEN A,KOCH DG,LEE WM. Drug-induced acute liver failure:Results of a US multicenter,prospective study[J].Hepatology,2010,52(6):2065-2076.

[4] SHEN T,LIU YX,SHANG J,et al. Incidence and etiology of drug-induced liver injury in mainland China[J]. Gastroenterology,2019,156(8):2230-2241.

[5] 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.

[6] Drug-induced Liver Disease Study Group,Chinese Society of Hepatology,Chinese Medical Association. Guidelines for the management of drug-induced liver injury[J]. J Clin Hepatol,2015,31(11):1752-1769.(in Chinese)中华医学会肝病学分会药物性肝病学组．药物性肝损伤诊治指南[J]．临床肝胆病杂志，2015,31(11):1752-1769.

[7] 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.

[8] LUCENA MI,ANDRADE RJ,KAPLOWITZ N,et al. Phenotypic characterization of idiosyncratic drug-induced liver injury:The influence of age and sex[J]. Hepatology,2009,49(6):2001-2009.

[9] SAADI T,WATERMAN M,YASSIN H,et al. Metformin-induced mixed hepatocellular and cholestatic hepatic injury:Case report and literature review[J]. Int J Gen Med,2013,6:703-706.

[10] GONZALEZ I,CHATTERJEE D. Histopathological features of drug-induced liver injury secondary to osimertinib[J]. Front Pharmacol,2019,6(2):1093.

[11] NAIDOO K,HASSAN-MOOSA R,MLOTSHWA P,et al. High rates of drug-induced liver injury in people living with hiv coinfected with tuberculosis(TB)irrespective of antiretroviral therapy timing during antituberculosis treatment:Results from the starting antiretroviral therapy at three points in TB trial[J].Clin Infect Dis,2019,10(17):1537-6591.

[12] DEV K,SUMITA V. Drug-induced liver injury[J]. Clin Med,2016,16(2):104-109.

[13] KAPLOWITZ N. Idiosyncratic drug hepatotoxicity[J]. Nat Rev Drug Discov,2005,4(6):489-499.

[14] RUSSMANN S,JETTER A,KULLAK-UBLICK GA. Pharm acogenetics of drug-induced liver injury[J]. Hepatology,2010,52(2):748-761.

[15] AHMAD S,AUDREY B,MATTHEW B,et al. Rho-kinase/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs[J]. Sci Rep,2016,12(6):24709

[16] RUSSMANN S,KULLAK-UBLICK GA,GRATTAGLIANO I.Current conceps of mechanisms in drug-induced hepatotoxicity[J]. Curr Med Chem,2009,16(23):3041-3053.

[17] GUENGERICH FP. Mechanisms of drug toxicity and relevance to pharmaceutical development[J]. Eur J Drug Metab Pharmacokinet,2011,26(1):3-14.

[18] BEGRICHE K,KARIMA J,ROBIN MA,et al. Drug-induced toxicity on mitochondria and lipid metabolism:Mechanistic diversity and deleterious consequences for the liver[J]. Hepatology,2011,54(4):773-794.

[19] MITCHELL R,MCGILL C,DAVID W,et al. Acetam inopheninduced liver injury in rats and m ice:Comparison of protein adducts,mitochondrial dysfunction,and oxidative stress in the m echanism of toxicity[J]. Toxicol Appl Pharm acol,2012,264(3):387-394.

[20] CHIPINDA I,HETTICK JM,SIEGEL PD. Haptenation:Chemical reactivity and protein binding[J]. J Allergy(Cairo),2011,2011:839682.

[21] UETRECHT J. Idiosyncratic drug reactions:Past,present,and future[J]. Chem Res Toxicol,2008,21(1):84-92.

[22] SATOH H,MARTIN BM,SCHULICK AH,et al. Human antiendoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase[J]. Proc Natl Acad Sci U S A,1989,86(1):322-326.

[23] AITHAL GP,RAMSAY L,DALY AK,et al. Hepatic adducts,circulating antibodies,and cytokine polymorphisms in patients with diclofenac hepatotoxicity[J]. Hepatology,2004,39(5):1430-1440.

[24] JENKINS RE,MENG X,ELLIOTT VL,et al. Characterisation of flucloxacillin and 5-hydroxymethyl flucloxacillin haptenated HAS in vitro and in vivo[J]. Proteomics Clin Appl,2009,3(6):720-729.

[25] CALLAN HE,JENKINS RE,MAGGS JL,et al. Multiple adduction reactions of nitroso sulfamethoxazole with cysteinyl residues of peptide and proteins:Implications for hapten formation[J]. Chem Res Toxicol,2009,22(5):937-948.

[26] DALY AK,DONALDSON PT,BHATNAGAR P,et al. HLA-B*5701 genotype is a m ajor determ inant of drug-induced liver injury due to flucloxacillin[J]. Nat Genet,2009,41(7):816-819.

[27] MONSHI MM,FAULKNER L,GIBSON A,et al. HLA-B*57∶01-restricted activation of drug-specific T cells provides the immunological basis for flucloxacillin-induced liver injury[J]. Hepatology,2013,57(2):727-739.

[28] CAI Y,YI J,ZHOU C,et al. Pharmacogenetic study of drug-metabolising enzyme polymorphisms on the risk of anti-tuberculosis drug-induced liver injury:A meta-analysis[J].PLo S One,2012,7(10):e47769.

[29] WANG L,ZHAO XY,MA H. Pathological features of drug-induced liver injury[J]. Chin Hepatol,2017,22(9):837-840.(in Chinese)王岚，赵新颜，马红．药物性肝损伤的病理学特征[J]．肝脏，2017,22(9):837-840.

[30] YU YC,FAN Y,CHENG CW. Criteria of chronic drug-induled liver injury:3 or 6 months or 1 year?[J]. Chin Hepatol,2017,22(2):97-100.(in Chinese)于乐成，范晔，陈成伟．药物性肝损伤慢性化判断标准:3或6个月还是1年?[J]．肝脏，2017,22(2):97-100.

[31] CHALASANI NP,HAYASHI PH,BONKOVSKY HL,et al. ACG clinical guideline:The diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol,2014,109(7):950-966.

[32] DANAN G,BENICHOU C. Causality assessment of adverse reactions to drugs I. A novel method based on the conclusions of international consensus meetings:Application to drug induced liver injuries[J]. Clin Epidemiol,1993,46(11):1323-1330.

[33] YU YC,FAN Y,CHEN CW. Diagnosis and treatment of druginduced liver injury[J]. J Clin Hepatol,2018,34(6):1160-1165.(in Chinese)于乐成，范晔，陈成伟．药物性肝损伤的诊断和治疗[J]．临床肝胆病杂志，2018,34(6):1160-1165.

[34] LI XF,LIAN JS,WANG YY,et al. The serum metabolomics research of drug induced liver injury based on ultra performance liquid chromatography-mass spectrometry[J]. Chin J Microecol,2013,25(6):625-629,638.(in Chinese)李小芬，连江山，王银银，等．基于超高效液相色谱质谱的药物性肝损害患者血清代谢组学研究[J]．中国微生态学杂志，2013,25(6):625-629,638.

[35] KIM JM,RYU SH,KIM S,et al. Pattern recognition analysis For hepatotoxicity induced by acetaminophen using plasma and urinary 1H NMR-based metabolomics in humans[J].Anal Chem,2013,85(23):11326-11334.

[36] GONZALEZ E,van LIEMPD S,CONDE-VANCELLS J,et al.Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver injury reveals potential biomarkers for hepato-toxicity[J]. Metabolomics,2012,8(6):n997-n1011.

[37] XIONG YH,YANG L,WANG ZT. Gas chromatography masss pectrometry based profiling of serum fatty acidsin acetaminophen-induced liver injured rats[J]. Applied Toxicology,2014,34(2):149-157.(in Chinese)熊以恒，杨琳，王志泰．气相色谱-质谱联用对乙酰氨基酚引起的肝损伤大鼠血清脂肪酸的分析[J]．应用毒理学杂志，2014,34(2):149-157.

[38] 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,2017,1(11):1-2.

[39] KULLAKUBLICK G,RADE RJ,ME RZM,et al. Drug-induced liver injury:Recent advances in diagnosis and risk as sessment[J]. Gut,2017,66(6):1154-1164.

[40] CHURCHRJ,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.

[41] STEPHANIE PD,JASON A. Review of drug-induced liver injury[J]. J Nurse Practitioners,2015,11(2):270-271.

[42] HOOFNAGLE JH,SERRANO J,KNOBEN JE,et al. LiverTox:A website on drug-induced liver injury[J]. Hepatology,2013,57(3):873-874.

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