药物性肝损伤治疗的进展与困惑

陈帅; 杨长青

doi:10.3969/j.issn.1001-5256.2021.11.001

药物性肝损伤治疗的进展与困惑

DOI: 10.3969/j.issn.1001-5256.2021.11.001

陈帅,
杨长青^,

同济大学附属同济医院消化内科，上海 200065

基金项目:

国家自然科学基金项目 (81670571);

国家自然科学基金项目 (81820108006);

上海市临床重点专科建设项目 (SHSLCZDZK06801);

上海申康三年行动计划重大临床研究项目 (SHDC2020CR2030B)

详细信息

通信作者:
杨长青：cqyang@tongji.edu.cn

中图分类号: R575
计量
- 文章访问数: 865
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- 被引次数: 0
出版历程
- 收稿日期: 2021-08-30
- 录用日期: 2021-08-30
- 出版日期: 2021-11-20

Drug-induced liver injury: Advances and confusions in treatment

Shuai CHEN,
Changqing YANG^,

Department of Gastroenterology, Tongji Hospital Affiliated to Tongji University, Shanghai 200065, China

Research funding:

National Natural Science Foundation of China (81670571);

National Natural Science Foundation of China (81820108006);

Shanghai Clinical Key Specialty Project (SHSLCZDZK06801);

Clinical Research Plan of SHDC (SHDC2020CR2030B)

摘要

摘要: 药物性肝损伤(DILI)是最常见、最严重的药物不良反应之一，严重者可引起急性肝衰竭甚至死亡。DILI发病机制尚未完全阐明，个体差异较显著，晚期DILI除肝移植外尚无有效的治疗方法，因此早期诊断、精准治疗显得尤为重要。现就近年来DILI治疗领域重要研究进展和难点问题进行述评。
- 化学性与药物性肝损伤 /
- 治疗学 /
- 预后
Abstract: Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions and can lead to acute liver failure and even death in severe cases. The pathogenesis of DILI has not been fully clarified, and there is significant individual difference. There is no effective treatment for advanced DILI except liver transplantation, and therefore, early diagnosis and precise treatment are of particular importance. This article reviews the important research advances and difficult issues in the treatment of DILI in recent years.
- Chemical and Drug Induced Liver Injury /
- Therapeutics /
- Prognosis

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参考文献(32)

[1]	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. DOI: 10.3969/j.issn.1001-5256.2015.11.002. 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. DOI: 10.3969/j.issn.1001-5256.2015.11.002.
[2]	BJÖRNSSON ES, BERGMANN OM, BJÖRNSSON HK, et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland[J]. Gastroenterology, 2013, 144(7): 1419-1425, 1425. e1-3; quiz e19-20. DOI: 10.1053/j.gastro.2013.02.006.
[3]	BJÖRNSSON ES. Epidemiology and risk factors for idiosyncratic drug-induced liver injury[J]. Semin Liver Dis, 2014, 34(2): 115-122. DOI: 10.1055/s-0034-1375953.
[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. DOI: 10.1053/j.gastro.2019.02.002.
[5]	HUNT CM, PAPAY JI, STANULOVIC V, et al. Drug rechallenge following drug-induced liver injury[J]. Hepatology, 2017, 66(2): 646-654. DOI: 10.1002/hep.29152.
[6]	XU CF, JOHNSON T, WANG X, et al. HLA-B*57: 01 Confers Susceptibility to pazopanib-associated liver injury in patients with cancer[J]. Clin Cancer Res, 2016, 22(6): 1371-1377. DOI: 10.1158/1078-0432.CCR-15-2044.
[7]	WATKINS PB, LEWIS JH, KAPLOWITZ N, et al. Clinical pattern of tolvaptan-associated liver injury in subjects with autosomal dominant polycystic kidney disease: Analysis of clinical trials database[J]. Drug Saf, 2015, 38(11): 1103-1113. DOI: 10.1007/s40264-015-0327-3.
[8]	BANIASADI S, EFTEKHARI P, TABARSI P, et al. Protective effect of N-acetylcysteine on antituberculosis drug-induced hepatotoxicity[J]. Eur J Gastroenterol Hepatol, 2010, 22(10): 1235-1238. DOI: 10.1097/MEG.0b013e32833aa11b.
[9]	KNOWLES SR, SHAPIRO LE, SHEAR NH. Anticonvulsant hypersensitivity syndrome: Incidence, prevention and management[J]. Drug Saf, 1999, 21(6): 489-501. DOI: 10.2165/00002018-199921060-00005.
[10]	BORLAK J, van BÖMMEL F, BERG T. N-acetylcysteine and prednisolone treatment improved serum biochemistries in suspected flupirtine cases of severe idiosyncratic liver injury[J]. Liver Int, 2018, 38(2): 365-376. DOI: 10.1111/liv.13538.
[11]	KAN M, HIMES BE. Insights into glucocorticoid responses derived from omics studies[J]. Pharmacol Ther, 2021, 218: 107674. DOI: 10.1016/j.pharmthera.2020.107674.
[12]	DARNELL EP, MOORADIAN MJ, BARUCH EN, et al. Immune-related adverse events (irAEs): Diagnosis, management, and clinical pearls[J]. Curr Oncol Rep, 2020, 22(4): 39. DOI: 10.1007/s11912-020-0897-9.
[13]	NISHIDA N, KUDO M. Liver damage related to immune checkpoint inhibitors[J]. Hepatol Int, 2019, 13(3): 248-252. DOI: 10.1007/s12072-018-9921-7.
[14]	TUJIOS SR, LEE WM. Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy[J]. Liver Int, 2018, 38(1): 6-14. DOI: 10.1111/liv.13535.
[15]	WAN YM, WU JF, LI YH, et al. Prednisone is not beneficial for the treatment of severe drug-induced liver injury: An observational study (STROBE compliant)[J]. Medicine (Baltimore), 2019, 98(26): e15886. DOI: 10.1097/MD.0000000000015886.
[16]	MAO YM, ZENG MD, CHEN Y, Et al. Magnesium isoglycyrrhizinate in the treatment of chronic liver diseases: A randomized, double-blind, multi-doses, active drug controlled, multi-center study[J]. Chin J Hepatol, 2009, 17(11): 847-851. DOI: 10.3760/cma.j.issn.1007-3418.2009.11.013. 茅益民, 曾民德, 陈勇, 等. 异甘草酸镁治疗ALT升高的慢性肝病的多中心、随机、双盲、多剂量、阳性药物平行对照临床研究[J]. 中华肝脏病杂志, 2009, 17(11): 847-851. DOI: 10.3760/cma.j.issn.1007-3418.2009.11.013.
[17]	WANG Y, WANG Z, GAO M, et al. Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug-induced liver injury: A phase Ⅱ trial[J]. Liver Int, 2019, 39(11): 2102-2111. DOI: 10.1111/liv.14204.
[18]	ZHAO Z, BAO L, YU X, et al. Acute vanishing bile duct syndrome after therapy with cephalosporin, metronidazole, and clotrimazole: A case report[J]. Medicine (Baltimore), 2017, 96(36): e8009. DOI: 10.1097/MD.0000000000008009.
[19]	GU J, TANG SJ, TAN SY, et al. An open-label, randomized and multi-center clinical trial to evaluate the efficacy of Silibinin in preventing drug-induced liver injury[J]. Int J Clin Exp Med, 2015, 8(3): 4320-4327.
[20]	LUANGCHOSIRI C, THAKKINSTIAN A, CHITPHUK S, et al. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury[J]. BMC Complement Altern Med, 2015, 15: 334. DOI: 10.1186/s12906-015-0861-7.
[21]	ASGARSHIRAZI M, SHARIAT M, SHEIKH M. Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury: A randomized clinical trial[J]. Hepatobiliary Pancreat Dis Int, 2017, 16(3): 296-302. DOI: 10.1016/s1499-3872(16)60142-x.
[22]	DEVARBHAVI H, AITHAL G, TREEPRASERTSUK S, et al. Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines[J]. Hepatol Int, 2021, 15(2): 258-282. DOI: 10.1007/s12072-021-10144-3.
[23]	NAIQIONG W, LIANSHENG W, ZHANYING H, et al. A multicenter and randomized controlled trial of bicyclol in the treatment of statin-induced liver injury[J]. Med Sci Monit, 2017, 23: 5760-5766. DOI: 10.12659/msm.904090.
[24]	SALIBA F, CAMUS C, DURAND F, et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: A randomized, controlled trial[J]. Ann Intern Med, 2013, 159(8): 522-531. DOI: 10.7326/0003-4819-159-8-201310150-00005.
[25]	LARSEN FS, SCHMIDT LE, BERNSMEIER C, et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial[J]. J Hepatol, 2016, 64(1): 69-78. DOI: 10.1016/j.jhep.2015.08.018.
[26]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-induced liver injury[J]. J Hepatol, 2019, 70(6): 1222-1261. DOI: 10.1016/j.jhep.2019.02.014.
[27]	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. DOI: 10.1038/ajg.2016.114.
[28]	ADAM R, KARAM V, CAILLIEZ V, et al. 2018 Annual Report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation[J]. Transpl Int, 2018, 31(12): 1293-1317. DOI: 10.1111/tri.13358.
[29]	WANG J, MA Z, NIU M, et al. Evidence chain-based causality identification in herb-induced liver injury: Exemplification of a well-known liver-restorative herb Polygonum multiflorum[J]. Front Med, 2015, 9(4): 457-467. DOI: 10.1007/s11684-015-0417-8.
[30]	ZHAO L, WANG Y, ZHANG Y. The potential diagnostic and therapeutic applications of exosomes in drug-induced liver injury[J]. Toxicol Lett, 2021, 337: 68-77. DOI: 10.1016/j.toxlet.2020.11.021.
[31]	MOMEN-HERAVI F, BALA S, BUKONG T, et al. Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages[J]. Nanomedicine, 2014, 10(7): 1517-1527. DOI: 10.1016/j.nano.2014.03.014.
[32]	POSSAMAI LA, MCPHAIL MJ, KHAMRI W, et al. The role of intestinal microbiota in murine models of acetaminophen-induced hepatotoxicity[J]. Liver Int, 2015, 35(3): 764-773. DOI: 10.1111/liv.12689.