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Frontiers of Medicine >> 2015, Volume 9, Issue 4 doi: 10.1007/s11684-015-0417-8

Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb

1. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
2. Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
3. Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing 100039, China
4. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China
5. Integrative Medical Center, 302 Military Hospital, Beijing 100039, China
6. Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
7. Diagnosis and Treatment Center of Western and Chinese Medicine for Liver Diseases, 302 Military Hospital, Beijing 100039, China
8. Institute of Clinical Pharmacology, Central South University, Changsha 410008, China

Accepted: 2015-10-09 Available online: 2015-11-26

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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.

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