RUCAM in Drug and Herb Induced Liver Injury: The Update

Gaby Danan, Rolf Teschke, Gaby Danan, Rolf Teschke

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.

Keywords: CIOMS; RUCAM; causality assessment; dietary supplements; drug hepatotoxicity; drug induced liver injury; drugs; herb induced liver injury; herbal hepatotoxicity; herbs.

Figures

Figure 1
Figure 1
Classification of liver injury required for causality assessment of suspected DILI and HILI cases by the updated RUCAM. Note above: ALP from hepatic origin only. Abbreviations: ALP, alkaline phosphatase; ALT, Alanine aminotransferase; DILI, Drug-induced liver injury; HILI, Herb-induced liver injury; N, Upper limit of normal; R, Ratio; RUCAM, Roussel Uclaf Causality Assessment Method.
Figure 2
Figure 2
Missed diagnoses in cases of initially suspected hepatotoxicity by synthetic drugs or herbs. Adapted from previous reports [31,32], which provide the respective references for each missed diagnosis listed above. Abbreviations: CMV, Cytomegalovirus; EBV, Epstein Barr virus; HSV Herpes simplex virus; LKM, Liver kidney microsomes; SMA, Smooth muscle antibodies; VZV, Varicella zoster virus.

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