Exploring new risk signals and susceptibility factors of traditional Chinese medicine-induced hepatotoxicity based on big data from adverse reaction monitoring

doi:10.19803/j.1672-8629.20230779

Abstract

Abstract: Objective To explore the method of discovering signals of hepatotoxicity risk in traditional Chinese medicine (TCM) based on national adverse reaction monitoring big data, preliminarily screen risky varieties, and analyze the susceptible factors of liver damage based on the “ Trielement Injury Hypothesis ” theory. Methods Retrospective analysis of adverse drug reaction (ADR) reports related to TCM-induced drug-induced liver injury (DILI) collected between 2012 and 2016. Identify suspicious TCM varieties and predict the susceptible factors for liver damage in these varieties. Results A total of 1 901 ADR reports（1 719 patients) of TCM-induced DILI were collected, and 237 suspicious TCM varieties were newly discovered. Traditional Chinese medicine used for anti-tumor purposes had the highest incidence of DILI. The oral route of administration accounted for the largest proportion (71.70%), with a median latency period of 13.00 days, and the majority of cases had a latency period of 0 to 7 days (34.46%). Analysis based on the “ Trielement Injury Hypothesis ”theory revealed that the TCM varieties suspected of causing DILI were related to the body’s state, the drugs themselves, and the medication environment. Conclusion Discovery of a series of TCM risk signals requires further confirmation of the risk and analysis of the causal mechanisms.

Key words: traditional Chinese medicine, adverse drug reactions, Trielement Injury Hypothesis, liver injury, anti-tumor, risk signals

CLC Number:

GUO Longxin, GAO Yunjuan, WU Chengzhao, LONG Minjuan, ZHU Shengkai, SONG Haibo, ZHAO Xu, XIAO Xiaohe. Exploring new risk signals and susceptibility factors of traditional Chinese medicine-induced hepatotoxicity based on big data from adverse reaction monitoring[J]. Chinese Journal of Pharmacovigilance, 2024, 21(1): 15-19.

Add to citation manager EndNote|Ris|BibTeX

URL: https://www.zgywjj.com/EN/10.19803/j.1672-8629.20230779

https://www.zgywjj.com/EN/Y2024/V21/I1/15

References

[1] LI X, TANG J, MAO Y.Incidence and risk factors of drug-induced liver injury[J]. Liver International, 2022, 42(9): 1999-2014.
[2] PAN X, ZHOU J, CHEN Y, et al.Classification, hepatotoxic mechanisms, and targets of the risk ingredients in traditional Chinese medicine-induced liver injury[J]. Toxicology Letters, 2020, 323: 48-56.
[3] HUANG LT, LU SJ, LU CP.Current state and development trend of pharmacovigilance in China[J]. Pharmaceutical and Clinical Research(药学与临床研究), 2014, 22(1): 96-99.
[4] XIE TT, GUO DH.Research and progress of drug evaluation at home and abroad[J]. Chinese Journal of Drug Application and Monitoring(中国药物应用与监测), 2019, 16(4): 191-195.
[5] WANG JB, ZHU Y, BAI ZF, et al.Branch committee of hepatobiliary diseases and branch committee of chinese patent medicines, China association of chinese medicine. guidelines for the diagnosis and management of herb-induced liver injury[J]. Chinese Journal of Integrative Medicine, 2018, 24(9): 696-706.
[6] XIAO XX, ZHAO X, BAI ZF, et al.New outlook on safety of traditional Chinese medicine: concept and practice[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2023, 48(10): 2557-2564.
[7] World Health Organization, UMC. The use of the WHO-UMC system for standardised case causality assessment[EB/OL].(2018-04-06)[2023-12-27]. https://who-umc.org/media/164200/who-umc-causality-assessment_new-logo.pdf.
[8] GUO YM, TU C, HE Q, et al.Safety administration strategy for heshouwu(polygoni multiflori radixbased on properties and actions of Chinese medicine[J]. Journal of Traditional Chinese Medicine(中医杂志), 2018, 59(9): 721-724.
[9] PENG SY, XIE YM, WANG ZF, et al.Analysis of adverse reactions of Xianling Gubao preparation based onreal world SRS data[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2020, 45(10): 2316-2321.
[10] HUANG Y, LIU YL, MA RR, et al.Clinical case analysis and disassembled prescription study of liver injuryrelated to Xianling Gubao[J]. Acta Pharmaceutica Sinica(药学学报), 2021, 56(1): 266-273.
[11] GAO Y, SHI W, TU C, et al.Immunostimulatory activity and structure-activity relationship of epimedin B from Epimedium brevicornu Maxim[J]. Frontiers in Pharmacology, 2022, 13: 1015846.
[12] WANG Y, XU G, WANG Z, et al.Psoralidin, a major component of Psoraleae Fructus, induces inflammasome activation and idiosyncratic liver injury[J]. International Immunopharmacol, 2021, 92: 107352.
[13] YAN BH, NIU Q, FU ZJ, et al.Efficacy and mechanism of danlu tongdu tablets on lumbar disc herniation with kidney deficiency and stasis syndrome[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2019, 25(22): 66-71.
[14] JEZEK J, SEPITKA J, DANIEl M, et al.The role of vascularization on changes in ligamentum flavum mechanical properties and development of hypertrophy in patients with lumbar spinal stenosis[J]. The Spine Journal: Official Journal of the North American Spine Society, 2020, 20(7): 1125-1133.
[15] ZHANG H, YANG Y, GUO F, et al.Danlu tongdu tablets: preclinical safety evaluation and mechanism of hepatotoxicity[J]. Frontiers in Pharmacology, 2022, 13: 1023379.
[16] ZHANG M, LIANG FN, SUN YW, et al.Research progress on chemical constituents, pharmacological effects and clinical application of eucommia ulmoides[J]. Chinese Traditional and Herbal Drugs(中草药), 2023, 54(14): 4740-4761.
[17] WANG D, WANG K, SUI D, et al.Effects of tetrahydroberberine and tetrahydropalmatine on hepatic cytochrome P450 expression and their toxicity in mice[J]. Chemico-Biological Interactions, 2017, 268: 47-52.
[18] ZHU Y, LI YG, WANG Y, et al.Clinical analysis of 595 cases of liver injury caused by Chinese medicine[J]. Chinese Journal of Integrated Traditional and Western Medicine(中国中西医结合杂志), 2016, 36(1): 44-48.
[19] LIN YX, HE XB.Clinical features of drug-induced liver injury and related risk factors[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2018, 34(6): 1237-1241.
[20] LIU R, XIN XJ.Research advances in pathogenesis, risk factors, monitoring, and retreatment of drug-induced liver injury[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2023, 39(4): 968-973.
[21] ZHANG LX, MENG L, ZHANG H.Analysis of 327 reports of new adverse drug reactions[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2023, 20(10): 1159-1162.
[22] ZHANG D.Study on drug-induced liver injury based on literature analysis[D]. Changsha: Hunan University of Chinese Medicine, 2018.
[23] Center for Drug Reevaluation, National Medicinal Products Administration. Drug Adverse Reaction Information Bulletin(Issue 72) Cautioning the Risk of Liver Injury Caused by Xianling Gubao Oral Preparations[EB/OL].(2016-12-09)[2023-12-01]. https://www.cdr-adr.org.cn/drug_1/aqjs_1/drug_aqjs_xxtb/201612/t20161209_36818.html.
[24] Center for Drug Reevaluation, National Medicinal Products Administration. Drug Adverse Reaction Information Bulletin(Issue 61) Attention to the Risk of Liver Injury Caused by Oral Administration of Polygonum multiflorum and its Formulations[EB/OL].(2014-07-19)[2023-12-01]. https://www.cdr-adr.org.cn/drug_1/aqjs_1/drug_aqjs_xxtb/201407/t20140719_36830.html.
[25] National Medical Products Administration. Announcement from the Administration on the Revision of Package Inserts for Four Varieties of Medicines, including Jinyu capsules[EB/OL].(2018-02-05)[2023-12-01]. https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypshmshxdgg/20180205170801445.html.
[26] LIU JC, ZHANG F, CHEN Z, et al.8 cases of liver injury caused by Pudilan anti-inflammatory preparations and literature review[J]. Central South Pharmacy(中南药学), 2021, 19(12): 2710-2715.
[27] LU DW.Analysis of adverse drug reaction reports of Chinese medicines[J]. Journal of China Prescription Drug(中国处方药), 2017, 15(2): 65-66.
[28] Center for Drug Reevaluation, National Medicinal Products Administration. Annual report of national adverse drug reaction monitoring(2022)[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2023, 20(6): 712-719.
[29] CHENG Y, WANG JH, XIA K, et al.Retrospective analysis of 656 patients with drug-induced liver injury[J]. Evaluation and Analysis of Drug-Use in Hospitals of China(中国医院用药评价与分析), 2020, 20(7): 885-888.
[30] SU FY, PAN E, ZHUO LG, et al.Analysis of 5 066 cases of drug-induced liver injury from 570 medical lnstitutions in Shandong[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2021, 18(8): 784-788.