I have carefully read the interesting study “Drug-induced liver injury: Relation between the R ratio and histopathology” by O.M. Ardila-Suárez et al., published in this journal. The authors state that the diagnosis of drug-induced liver injury (DILI) is based on the ruling out of other potential causes and on the clinical capacity to establish causality between the potentially hepatotoxic substance and abnormal liver biochemical profile results and that neither the Roussel-Uclaf hepatotoxicity causality assessment method (RUCAM) nor other methods were applied because of their limitations for use in retrospective studies.1

The RUCAM emerged from a consensus meeting on adverse reactions to drugs, at which it was proposed as a method for evaluating causality. It scores different criteria for studying the probability of causality of a drug: time to onset and course of the reaction; risk factors, such as age, alcohol use, or pregnancy; the search for other causes or concomitant medications; prior knowledge of toxicity; response to rechallenge; serum levels of the medication; and validated laboratory tests. In practice, the overall scoring range would be from –5 to +13, signifying the total of arguments for or against the drug as the cause of liver injury. A score of 0 or less excludes causality probability, it is unlikely with a score of 1-2, possible with a score of 3-5, probable with a score of 6-8, and highly probable with a score over 9. Table 1 shows a model of the RUCAM, adapted from the original publication by Danan and Benichou2 (Annex. Supplementary material).

Articles analyzing the use of the RUCAM conclude that the causality assessment method adapts to prospective and retrospective studies and is a reliable tool in the context of DILI and herb-induced liver injury (HILI) for establishing the association of the cases with the suspected offending drug or herb. Thus, RUCAM should be systematically implemented and included in the clinical history of patients suspected of presenting with DILI.3

RUCAM is a validated method that is useful as a diagnostic algorithm for attaining a probable or highly probable causality score for the suspected drug. It provides a solid causality assessment of drugs suspected of involvement in DILI, which is of particular significance, given that the management of idiosyncratic DILI is considered a therapeutic challenge.4

The RUCAM appeared in 1993 and is a widely used tool worldwide for diagnosing DILI and HILI in a large number of epidemiologic studies, case reports, and case series. The RUCAM has been shown to have high sensitivity (86%) and specificity (89%), with elevated positive predictive values (93%) and negative predictive values (78%). In addition, it has shown good reproducibility results and low interobserver variability. At present, the RUCAM continues to be the main standard for causality assessment methods when drug-induced or herb-induced liver injury is suspected.5