Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases

Abstract

Herb-induced liver injuries (HILI) by traditional herbal medicines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in worldwide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from mainland China, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, however, the following recommendations are given: (1) preference of prospective study design with use of the updated RUCAM version; (2) clear separation of HILI cohorts from those of other herbal products or DILI; (3) case series for epidemiology studies should contain many essential data, possibly also as supplementary material; (4) otherwise, preference of single case reports providing individual case data and RUCAM-based causality gradings, and applying liver test threshold values; and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.

Effects and safety of herbal medicines among community-dwelling residents during COVID-19 pandemic: A large prospective, randomized controlled trial (RCT)

“…Although herbal medicine is considered as a safe way to boost the immune system and has very few side effects, safety should always be the top priority in the use of herbal medicines, as it might cause herb-induced liver injury (HILI) to patients (Xiao et al, 2018). According to Teschke et al, from 2006 to 2019, there were 21 published studies of HILI cases assessed for causality using the Roussel Uclaf Causality Assessment Method (RUCAM) in China ( Teschke et al, 2020 ). However, these studies did not report any HILI cases caused by the herb medicines used in this specific trial.…”

Worldwide Use of RUCAM for Causality Assessment in 81,856 Idiosyncratic DILI and 14,029 HILI Cases Published 1993–Mid 2020: A Comprehensive Analysis

“…Liver injury is either idiosyncratic, due to the interaction between the exogenous synthetic chemical or phytochemical and a susceptible individual with some genetic factor(s), or it is intrinsic due to chemical overdose [ 11 , 12 , 13 ]. In the present analysis, idiosyncratic injury is considered, as opposed to intrinsic liver injury most commonly observed with overdosed drugs such as acetaminophen [ 22 ].…”

“…During 2016, there was a sharp increase with 933 HILI cases, mostly attributed to 866 cases from China published by Zhu et al [ 42 ]. As a reminder and outlined recently, herb induced liver injury with HILI as its acronym was first introduced and proposed as a specific term in the scientific literature only in 2011 [ 12 ]. This may explain retarded publications on HILI cases ( Figure 3 ).…”

“…The present scientometric study comprehensively analyzed the global knowledge base and specific emerging topics of DILI derived from 1995 publications in 79 countries and regions, with an impressive annual growth of reports between 2010 and 2019 and almost 340 studies published in 2020 [ 1 ]. In parallel, more and more publications on DILI and HILI cases refer to RUCAM (Roussel Uclaf Causality Assessment Method) for causality assessment [ 10 , 11 , 12 , 13 ]. The original RUCAM was first published in 1993 [ 14 ] and updated in 2016 [ 15 ] with additional information on its use and perspectives [ 16 , 17 ], which is now the preferred version to be used in future cases of DILI and HILI [ 15 ].…”

“…The original RUCAM was first published in 1993 [ 14 ] and updated in 2016 [ 15 ] with additional information on its use and perspectives [ 16 , 17 ], which is now the preferred version to be used in future cases of DILI and HILI [ 15 ]. It is widely recognized that causality assessment in DILI and HILI is a multifaceted approach [ 7 , 8 , 9 , 15 ], a real medical challenge, for which a diagnostic quantitative algorithm such as RUCAM is an easy tool for case evaluation [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ] to solve complex conditions [ 18 ].…”