Abstract
Among the causality assessment methods used for the diagnosis of drug-induced liver injury (DILI), Roussel Uclaf Causality Assessment Method (RUCAM) remains the most widely used not only for individual cases but also for prospective and retrospective studies worldwide. This first place is justified by the characteristics of the method such as precise definition and classification of the liver injury, which determines the right scale in the scoring system, precise definition of the seven criteria, and the validation approach based on cases with positive rechallenge. RUCAM is used not only for any types of drugs but also for herbal medicines causing herb-induced liver injury, (HILI) and dietary supplements. In 2016, the updated RUCAM provided further specifications of criteria and instructions to improve interobserver variability. Although this method was criticized for criteria such as the age and alcohol consumption, recent consensus meeting of experts has recognized their value and recommended their incorporation into any method. While early studies searching for DILI in large databases especially in electronic medical records were based on codes of diseases or natural language without causality assessment, the recommendation is now to include RUCAM in the search for DILI/HILI. There are still studies on DILI detection or the identification of biomarkers that take into consideration the cases assessed as “possible,” although it is well known that these cases reduce the strength of the association between the cases and the offending compound or the new biomarker to be validated. Attempts to build electronic RUCAM or automatized application of this method were successful despite some weaknesses to be corrected. In the future, more reflections are needed on an expert system to standardize the exclusion of alternative causes according to the clinical context. Education and training on RUCAM should be encouraged to improve the results of the studies and the day-to-day work in pharmacovigilance departments in companies or in regulatory agencies. It is also expected to improve RUCAM with biomarkers or other criteria provided that the validation process replaces expert opinion by robust standards such as those used for the original method.
Highlights
The diagnosis of drug-induced liver injury (DILI) as any other disease needs to be supported by strong criteria
The analysis of the current Roussel Uclaf Causality Assessment Method (RUCAM) use shows that the method is adapted to the clinical situations as well as to prospective and retrospective studies involving DILI or searching for DILI (Figure 1)
It was shown that RUCAM is adapted to liver injury induced by herbs or dietary supplements, which account for an increasing proportion of liver injuries especially in Asian countries
Summary
The diagnosis of drug-induced liver injury (DILI) as any other disease needs to be supported by strong criteria. The Roussel Uclaf Causality Assessment Method (RUCAM) was created and validated with positive rechallenge cases (reference in Danan and Teschke, 2016), but some confusion remains on its name. This came from insufficient reading or misunderstanding of the original article. Despite a slow start between 1993 and early 2000s, RUCAM became the most widely used method to support DILI diagnosis in different settings that prompted an updated version to further improve the results (Danan and Teschke, 2016). The objectives of this article are twofold: first, to describe, comment on, and highlight how the current utilization of RUCAM can be improved and, second, to consider the future applications of RUCAM beyond individual cases to detect hepatotoxicity of any types of compounds administered to humans
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