中草药相关肝损伤的管理与治疗

孙鑫; 罗琼; 杨涛; 刘成海

doi:10.12449/JCH240806

中草药相关肝损伤的管理与治疗

DOI: 10.12449/JCH240806

孙鑫^{1a, 2},
罗琼^1a,
杨涛^{1b, 2},
刘成海^{1a, 2, 3, , ,}

1a.
上海中医药大学附属曙光医院肝病研究所，上海 201203
1b.
上海中医药大学附属曙光医院心血管病研究所，上海 201203
2.
上海市中医临床重点实验室，上海 201203
3.
肝肾疾病病证教育部重点实验室，上海 201203

基金项目:

国家中医药管理局高水平中医药重点学科建设项目 (zyyzdxk-2023060);

上海市中医药事业发展三年行动计划 (ZY（2018-2020）-CCCX-5001);

上海市科学技术委员会科技创新行动计划医学创新研究专项 (20Z21900100);

上海市临床重点专科建设项目 (shslczdzk01201)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：孙鑫负责资料收集和撰写论文；罗琼参与资料收集和整理；杨涛负责指导撰写和修改论文；刘成海负责拟定写作思路、指导撰写文章并最后定稿。

详细信息

通信作者:
刘成海， chenghailiu@hotmail.com （ORCID： 0000-0002-1696-6008）

计量
- 文章访问数: 253
- HTML全文浏览量: 357
- PDF下载量: 82
- 被引次数: 0
出版历程
- 收稿日期: 2024-06-15
- 录用日期: 2024-07-05
- 出版日期: 2024-08-25

Management and treatment of herb-induced liver injury

Xin SUN^{1a, 2},
Qiong LUO^1a,
Tao YANG^{1b, 2},
Chenghai. LIU^{1a, 2, 3
, ,
,}

1a.
Institute of Liver Diseases，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China
1b.
Institute of Cardiovascular Disease，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China
2.
Shanghai Key Laboratory of Traditional Chinese Clinical Medicine，Shanghai 201203，China
3.
Key Laboratory of Liver and Kidney Diseases，Ministry of Education，Shanghai 201203，China

Research funding:

High-level Key Discipline Construction Project from State Administration of Traditional Chinese Medicine of China (zyyzdxk-2023060);

Shanghai TCM Development Three-Year Action Plan Project (ZY（2018-2020）-CCCX-5001);

Shanghai Science and Technology Innovation Action Plan Medical Innovation Research Special Project (20Z21900100);

Shanghai Key Specialty of Traditional Chinese Clinical Medicine (shslczdzk01201)

摘要

摘要: 由于我国中草药产品应用形式多样，使用人群广泛，用药情况复杂，近年来中草药相关肝损伤等不良反应事件频发，为进一步科学认识中草药相关肝损伤，规范其风险管理与防治措施，本文结合近年的临床研究进展与相关经验，对中草药相关肝损伤的风险管理、临床评价、预防及治疗展开论述。在中药研发生产、上市后的临床应用等多环节，建立涉及中药产品质量控制、患者安全教育、临床医师合理用药、定期监测、分级分型治疗等全方位的中草药相关肝损伤的管控体系，对于预防和处理肝损伤等不良反应事件非常重要，为中草药临床安全合理用药提供参考和借鉴。
- 中草药 /
- 化学性与药物性肝损伤 /
- 治疗学
Abstract: Due to the diverse application forms of Chinese herbal medicine products， the wide range of users， and the complex conditions of medication in China， adverse events including herb-induced liver injury （HILI） occur frequently in recent years. In order to further understand HILI and standardize its risk management and prevention and treatment measures， this article discusses the risk management， clinical evaluation， prevention， and treatment of HILI based on related clinical research advances and experience in recent years. In the multiple links of traditional Chinese medicine including production and clinical application after marketing， the establishment of a comprehensive control system is of great importance for the prevention and treatment of HILI and other adverse events， involving product quality control， patient safety education， rational drug use by clinicians， regular monitoring， and graded and classified treatment， which provides a reference for the rational and safe clinical use of Chinese herbal medicine in the future.
- Drugs， Chinese Herbal /
- Chemical and Drug Induced Liver Injury /
- Therapeutics

HTML全文

表 1 HILI药物治疗主要机制

Table 1. The main mechanisms of drug therapy for HILI

药物类别	药物名称	作用机制
保护肝细胞	N-乙酰半胱氨酸（NAC）	清除氧自由基
	甘草制剂	抗炎、抗氧化
	双环醇	抗炎、抗氧化
	多烯磷脂酰胆碱	增加肝细胞膜稳定性
	水飞蓟素	增加肝细胞膜稳定性、抗氧化
抗胆汁淤积	熊去氧胆酸	促进胆汁排泄
抗胆汁淤积	腺苷蛋氨酸	促进胆汁排泄、抗氧化
免疫抑制剂	激素	免疫抑制、抗炎
特殊药物	肝素	抗凝血
	去纤苷	促进纤维蛋白溶解
注：（1）对肝细胞损伤型HILI，可选用以降低ALT和/或AST为主的NAC（短疗程静脉注射NAC不推荐用于儿童）、甘草酸制剂、双环醇、水飞蓟素、多烯磷脂酰胆碱等抗炎保肝药治疗。（2）对胆汁淤积型HILI，可选用以降低ALP和/或GGT为主的熊去氧胆酸、腺苷蛋氨酸治疗。（3）对混合型HILI，可选择一种肝细胞保护剂加一种抗胆汁淤积药物联合治疗。（4）对于其他特殊类型的HILI，如含吡咯烷类生物碱等中药引起的肝窦阻塞综合征或肝小静脉闭塞症的肝血管损伤型HILI，在排除禁忌证后应尽早使用低分子肝素等抗凝药物，中-重度肝窦阻塞综合征HILI患者也可使用去纤苷治疗；何首乌等中药引起的特异质型HILI，在予以适当剂量和疗程的糖皮质激素治疗的同时，还应对症采取止吐药、止痒药和补液等支持性治疗^［5］。

下载: 导出CSV

参考文献(20)

[1]	Center for Drug Evaluation, National Medicine Products Administration. Guidelines for identification, management, and assessment of drug-induced liver injury in clinical trials[J]. J Clin Hepatol, 2023, 39( 8): 1811- 1816. DOI: 10.3969/j.issn.1001-5256.2023.08.007. 国家药品监督管理局药品审评中心. 临床试验中的药物性肝损伤识别、处理及评价指导原则[J]. 临床肝胆病杂志, 2023, 39( 8): 1811- 1816. DOI: 10.3969/j.issn.1001-5256.2023.08.007.
[2]	LI M, LI RR, LIU CH. Clinic diagnosis and treatment of herb-induced liver injury[J]. Chin J Pharmacovigil, 2023, 20( 2): 127- 131. DOI: 10.19803/j.1672-8629.20220661. 李盟, 李容容, 刘成海. 中草药引起肝损伤的临床诊治与用药[J]. 中国药物警戒, 2023, 20( 2): 127- 131. DOI: 10.19803/j.1672-8629.20220661.
[3]	Committee on DILI Prevention and Management, Chinese Medical Biotechnology Association; Study Group of Drug-Induced Liver Disease, Chinese Medical Association for the Study of Liver Diseases. Chinese guideline for diagnosis and management of drug-induced liver injury(2023 version)[J]. Chin J Gastroenterol, 2023, 28( 7): 397- 431. DOI: 10.3760/cma.j.cn501113-20230419-00176. 中国医药生物技术协会药物性肝损伤防治技术专业委员会, 中华医学会肝病学分会药物性肝病学组. 中国药物性肝损伤诊治指南(2023年版)[J]. 胃肠病学, 2023, 28( 7): 397- 431. DOI: 10.3760/cma.j.cn501113-20230419-00176.
[4]	World Health Organization. Key technical issues of herbal medicines with reference to interaction with other medicines[M]. Geneva: World Health Organization, 2021.
[5]	FONTANA RJ, LIOU I, REUBEN A, et al. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury[J]. Hepatology, 2023, 77( 3): 1036- 1065. DOI: 10.1002/hep.32689.
[6]	LIU YJ, RAN S, CHEN ZD, et al. Exploration of the standardized reporting procedure for drug-induced liver injury related to Chinese materia medica[J]. J Beijing Univ Tradit Chin Med, 2023, 46( 11): 1582- 1586. DOI: 10-3969/j.issn.1006-2157.2023.11.013. 刘玉娟, 冉姗, 陈志东, 等. 关于中药相关药物性肝损伤的规范化报告程序的探讨[J]. 北京中医药大学学报, 2023, 46( 11): 1582- 1586. DOI: 10-3969/j.issn.1006-2157.2023.11.013.
[7]	Chinese Society for Tuberculosis, Chinese Medical Association. Guidelines for the diagnosis and treatment of antituberculous drug-induced liver injury(2019 edition)[J]. Chin J Tuberc Respir Dis, 2019, 42( 5): 343- 356. DOI: 10.3760/cma.j.issn.1001-0939.2019.05.007. 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. DOI: 10.3760/cma.j.issn.1001-0939.2019.05.007.
[8]	LIU SY, LI M, TANG Y, et al. Research progress on the mechanism of liver injury by polygonum multiflorum and attenuation and synergism[J]. Cent South Pharm, 2024, 22( 4): 1008- 1015. DOI: 10.7539/j.issn.1672-2981.2024.04.028. 刘思雨, 李敏, 唐瑜, 等. 何首乌肝损伤机制及减毒方法研究进展[J]. 中南药学, 2024, 22( 4): 1008- 1015. DOI: 10.7539/j.issn.1672-2981.2024.04.028.
[9]	HE N, MA ZZ, WANG QY, et al. Euodiae Fructus(Wuzhuyu): Exploring traditional Chinese medicine compatibility for reducing toxicity[J]. Chin Tradit Herb Drugs, 2024, 55( 6): 1812- 1838. DOI: 10.7501/j.issn.0253-2670.2024.06.005. 何宁, 马珍珍, 王秋月, 等. 有毒中药吴茱萸及减毒配伍研究探讨[J]. 中草药, 2024, 55( 6): 1812- 1838. DOI: 10.7501/j.issn.0253-2670.2024.06.005.
[10]	ZHANG Y, WANG XY, DING ZH, et al. Systematic review on safety of Chinese medicines combined with Tripterygium wilfordii preparations in treatment of rheumatoid arthritis and exploration on underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity[J]. Chin J Exp Tradit Med Formulae, 2023, 29( 5): 1- 8. DOI: 10.13422/j.cnki.syfjx.20220943. 张依, 王晓月, 丁子禾, 等. 中药配伍雷公藤制剂治疗类风湿关节炎的安全性系统评价及其增效减毒网络调控机制[J]. 中国实验方剂学杂志, 2023, 29( 5): 1- 8. DOI: 10.13422/j.cnki.syfjx.20220943.
[11]	LIU Q, GUO YL, DONG TW, et al. Research progress on hepatotoxicity mechanism and attenuation methods of psoraleae fructus[J]. Chin J Exp Tradit Med Formulae, 2021, 27( 11): 233- 239. DOI: 10.13422/j.cnki.syfjx.20210626. 刘巧, 郭延丽, 董泰玮, 等. 补骨脂肝损伤机制及减毒方法研究进展[J]. 中国实验方剂学杂志, 2021, 27( 11): 233- 239. DOI: 10.13422/j.cnki.syfjx.20210626.
[12]	GE XX, ZHANG PP, WU Q, et al. Study on the toxic reduction and mechanism of Huangyaozi compatibility based on liver injury[J]. Mod Chin Med, 2023, 43( 3): 1- 5. DOI: 10.13424/j.cnki.mtcm.2023.03.001. 葛肖肖, 张盼盼, 仵琼, 等. 基于肝损伤的黄药子配伍减毒及其作用机制研究[J]. 现代中医药, 2023, 43( 3): 1- 5. DOI: 10.13424/j.cnki.mtcm.2023.03.001.
[13]	WANG T, SUN K, LI JY, et al. Study of triptolide on liver injury and detoxification strategy[J]. Chin J Exp Tradit Med Formulae, 2024, 30( 6): 196- 204. DOI: 10.13422/j.cnki.syfjx.20231126. 王婷, 孙珂, 李静颐, 等. 雷公藤甲素的肝损伤及减毒策略[J]. 中国实验方剂学杂志, 2024, 30( 6): 196- 204. DOI: 10.13422/j.cnki.syfjx.20231126.
[14]	CAO YJ. The study of molecular mechanism for liver injury induced by epimedium based on metabolomics and network toxicology[D]. Beijing: Beijing University of Chinese Medicine, 2021. 曹一佳. 基于代谢组学和网络毒理学初步探究淫羊藿引发肝损伤的分子机制[D]. 北京: 北京中医药大学, 2021.
[15]	WANG G, ZHANG D, CHEN X. Prophylactic treatment with Hugan Tablets for antituberculosis drug-induced liver injury: A systematic review and meta-analysis of randomized controlled trials[J]. Chin J Integr Tradit West Med Liver Dis, 2024, 34( 1): 42- 48. DOI: 10.3969/j.issn.1005-0264.2024.001.009. 王岗, 张丹, 陈新. 护肝片预防性治疗抗结核药物性肝损伤的Meta分析[J]. 中西医结合肝病杂志, 2024, 34( 1): 42- 48. DOI: 10.3969/j.issn.1005-0264.2024.001.009.
[16]	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;quiz967. DOI: 10.1038/ajg.2014.131.
[17]	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.
[18]	U.S. Department of Health and Human Service Food and Drug Administration, Center for Drug Evaluation and Research(CDER), Center for Biologics Evaluation and Research(CBER). Guidance for Industry: Drug-induced Liver Injury: Premarketing Clinical Evaluation[R/OL].( 2009-07). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation
[19]	Branch of Hepatobiliary Diseases, China Association of Chinese Medicine, Branch of Chinese Patent Medicine, China Association of Chinese Medicine. Guideline for diagnosis and treatment of herb-induced liver injury[J]. J Clin Hepatol, 2016, 32( 5): 835- 843. DOI: 10.3969/j.issn.1001-5256.2016.05.003. 中华中医药学会肝胆病分会, 中华中医药学会中成药分会. 中草药相关肝损伤临床诊疗指南[J]. 临床肝胆病杂志, 2016, 32( 5): 835- 843. DOI: 10.3969/j.issn.1001-5256.2016.05.003.
[20]	LI M, LUO Q, TAO YY, et al. Pharmacotherapies for drug-induced liver injury: A current literature review[J]. Front Pharmacol, 2021, 12: 806249. DOI: 10.3389/fphar.2021.806249.