RUCAM in Drug and Herb Induced Liver Injury: The Update

Abstract

RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common basic tool.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study

“…The plants associated with hepatic signs and symptoms in this study Camellia sinensis (L.) Kuntze (Bunchorntavakul, 2013;Mazzanti, 2009), Dioscorea villosa L. (Wojcikowski, 2008), and Mentha piperita L. (Akdogan, 2004) exist, the design of the present study does not allow to add further evidence, particularly if the plant was part of a multi-ingredient product. In addition, a causality assessment according to RUCAM (Roussel Uclaf Causality Assessment Method), which is the reference method for evaluating drug and herb induced liver injury (Danan, 2016), was not possible due to incomplete case information. This is for example the case for Dioscorea villosa L., which was involved in two of the four cases of hepatotoxicity.…”

“…This is for example the case for the ingested dose of a PFS or a plant, which could not always be recorded or specified in detail. In addition, this is the reason why causality assessment of hepatotoxicity cases according to RUCAM (Danan, 2016) was not possible.…”

Zoledronic Acid: A Mischievous Suspect for Liver Injury

“…Later during follow-up, laboratory investigations exhibited liver enzymes within the normal range. Furthermore, the causal relationship was established using Naranjo's algorithm (score -6) and Roussel Uclaf Causality Assessment Method (score -5), displayed a "probable" and "possible" association [21][22][23]. Furthermore, Hartwig's severity scale [24,25] and Thornton's preventability scale [26] demonstrated adverse drug reaction to being moderately severe and not preventable, respectively.…”

A great honor and a huge challenge for China: You-you TU getting the Nobel Prize in Physiology or Medicine

“…Some of the toxicities associated with herbal TCM are well understood or documented: Wang et al (2015) have described an experiment that proved kudzu root extractinduced hepatotoxicity; an experiment in rats showed that yuanhuapine-induced intestinal and hepatic toxicities were correlated with disturbance of amino acid metabolism, lipid metabolism, carbohydrate metabolism, and gut microflora (Chen et al, 2015); and, from 1992 to 2015, 693 cases have been reported for Chinese herbal hepatotoxicity . Hepatotoxicity by herbal TCM must be validly established using a causality assessment method that is specific for the liver and hepatotoxicity such as Roussel Uclaf Causality Assessment Method (RUCAM) (Danan and Teschke, 2016).…”