title: Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum.
abstract: Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury (DILI) in the United States. However, reliable methods to identify the DILI causality of some herbs, such as Heshouwu (dried root of Polygonum multiflorum), remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% (9/40) and 30.6% (45/147) of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% (19/20) of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin (heavy metals, pesticides, and mycotoxins) contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Wang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.|Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Ma
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Niu
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.|Integrative Medical Center, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Liang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Song
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Zhaofang
authors.initials: Z
authors.lastname: Bai
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Integrative Medical Center, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Meng
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Lushan
authors.initials: L
authors.lastname: Qin
authors.affiliation: Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Guangju
authors.initials: G
authors.lastname: Teng
authors.affiliation: Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Cao
authors.affiliation: Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, 100039, China.
authors.forename: Baosen
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Diagnosis and Treatment Center of Western and Chinese Medicine for Liver Diseases, 302 Military Hospital, Beijing, 100039, China. alyg100039@sina.com.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, 100039, China. bzouzs302@126.com.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Institute of Clinical Pharmacology, Central South University, Changsha, 410008, China. chhzhou2003@163.com.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Integrative Medical Center, 302 Military Hospital, Beijing, 100039, China. dpharmacy302@126.com.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Xiao
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D000068676:Fallopia multiflora / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D008111:Liver Function Tests / Q000379:methods; D008516:Medicine, Chinese Traditional / Q000379:methods; D055442:Metabolome; D018570:Risk Assessment; D013267:Stilbenes / Q000009:adverse effects*
chemical_list: D004365:Drugs, Chinese Herbal; D013267:Stilbenes
keywords: Chinese herbal medicine; Polygonum multiflorum; drug-induced liver injury; metabolomics; pharmacognosy; stilbene