Herb-induced liver injury (HILI) with 12,068 worldwide cases published with causality assessments by Roussel Uclaf Causality Assessment Method (RUCAM): an overview

Abstract

Herbal products including herbal medicines are worldwide used in large amounts for treating minor ailments and for disease prevention. However, efficacy of most herbal products has rarely been well documented through randomized controlled trials in line with evidence-based medicine concepts, which could be used to estimate the benefit/risk ratio. Instead, much better documented are adverse reactions such as liver injury associated with the consumption of some herbal products, so called herb-induced liver injury (HILI), which represents a clinical challenge. In order to establish HILI as valid diagnosis, the use of a diagnostic algorithms such as Roussel Uclaf Causality Assessment Method (RUCAM) is widely recommended, although physicians in some countries are reluctant to use RUCAM for their HILI cases.This review on worldwide HILI and RUCAM, developed as part of the artificial intelligence ideas, reveals that China is the leading country with 24 publications on HILI cases that were all assessed for causality using RUCAM, followed by Korea with 15 reports, Germany with 9 reports, the US with 7 reports, and Spain with 6 reports, whereas the remaining countries provided less than 4 reports. The total number of assessed HILI cases is 12,068 worldwide derived from 80 publications but in each report HILI case numbers were variable in a range from 1 up to 6,971. This figure compares with 46,266 cases of drug-induced liver injury (DILI) published worldwide from 2014 to early 2019 also assessed for causality by RUCAM. The original version of RUCAM was validated and established in 1993 and updated in 2016 that should be used in future HILI cases. RUCAM is an objective, structured, and validated method, specifically designed for liver injury. It is a scoring system including case data elements to be assessed and scored individually to provide a final score in five causality gradings. Among the 11,404/12,068 HILI (94.5%) cases assessable for evaluation, causality gradings were highly probable in 4.2%, probable in 15.5%, possible in 70.3%, and unlikely or excluded in 10.0%. To improve the future reporting of RUCAM based HILI cases, recommendations include the strict adherence to instructions outlined in the updated RUCAM and, in particular, to follow prospective data collection on the cases to ensure completeness of case data. In conclusion, RUCAM can well be used to assess causality in suspected HILI cases, and additional efforts are now required to increase the quality of the reported cases.

Metabolic Toxification of 1,2-Unsaturated Pyrrolizidine Alkaloids Causes Human Hepatic Sinusoidal Obstruction Syndrome: The Update

“…General agreement exists that the use of some plants or herbal medicine, whether they contain 1,2-unsaturated PAs or not, may create health problems, including liver injury, termed globally as herb-induced liver injury (HILI) [ 8 , 42 , 48 , 145 , 162 , 195 , 196 , 197 ]. However, liver injury in connection with the use of plants containing 1,2-unsaturated PAs is a special disease entity, further specified as HSOS [ 6 , 198 , 199 , 200 ], replacing the previous term “HVOD (hepatic veno-occlusive disease)” with “HSOS” upon suggestion by DeLeve et al [ 199 ].…”

“…RUCAM is worldwide used to assess causality in 95,885 cases of both DILI and HILI [ 234 ], with additional details provided for DILI [ 16 , 17 , 18 , 19 ] and HILI [ 42 , 196 , 225 ]. With respect to HILI including PA-HSOS, overall 14,029 RUCAM based cases were published until the mid of 2020 [ 234 ], among them were 28 PA-HSOS cases [ 211 , 217 ].…”

Safety of Anthroposophic Medicinal Products: An Analysis of Adverse Drug Reactions from German Pharmacovigilance Databases

“…These five cases were post hoc reassessed with respect to the possible occurrence of herb-induced liver injury (HILI) [ 37 ]. The assessment was based on the outcome variables a–o (cf.…”

“…The causal relationship between the ADRs had been classified as probable/likely (Patient #1 in Table 6) and not assessable (Patients #2-5 with altogether seven PTs). These five cases were post hoc reassessed with respect to the possible occurrence of herb-induced liver injury (HILI) [37]. The assessment was based on the outcome variables a-o (cf.…”

Levels and Health Risk of Pesticide Residues in Chinese Herbal Medicines

“…The risk assessment of herb-induced liver injury (HILI) for individual cases was achieved using the Roussel Uclaf Causality Assessment Method (RUCAM) (Danan Teschke, 2016) under the recommendations of the Chinese Society of Hepatology (GSH) (Yu et al, 2017). With the data provided for worldwide published 12,068 HILI cases (Teschke et al, 2020), the risk of liver injury associated with the use of CHMs was evidenced by using RUCAM to verify a causal relationship. The investigation of the causes of HILI is the focus of attention at present.…”