Opin vísindi

A revised electronic version of RUCAM for the diagnosis of DILI

A revised electronic version of RUCAM for the diagnosis of DILI

Title: A revised electronic version of RUCAM for the diagnosis of DILI
Author: Hayashi, Paul H
Lucena, M Isabel
Fontana, Robert J
Björnsson, Einar Stefán
Aithal, Guruprasad P
Barnhart, Huiman
Gonzalez-Jimenez, Andres
Yang, Qinghong
Gu, Jiezhun
Andrade, Raul J
... 1 more authors Show all authors
Date: 2022-07
Language: English
Scope: 14
Department: Other departments
Faculty of Medicine
Series: Hepatology; 76(1)
ISSN: 0270-9139
DOI: 10.1002/hep.32327
Subject: Meltingarlæknisfræði; Chemical and Drug Induced Liver Injury; Causality; Dyphylline; Reproducibility of Results; Humans; Electronics; Chemical and Drug Induced Liver Injury/diagnosis; Hepatology
URI: https://hdl.handle.net/20.500.11815/4089

Show full item record


Hayashi , P H , Lucena , M I , Fontana , R J , Björnsson , E S , Aithal , G P , Barnhart , H , Gonzalez-Jimenez , A , Yang , Q , Gu , J , Andrade , R J & Hoofnagle , J H 2022 , ' A revised electronic version of RUCAM for the diagnosis of DILI ' , Hepatology , vol. 76 , no. 1 , pp. 18-31 . https://doi.org/10.1002/hep.32327


BACKGROUND AND AIMS: Roussel Uclaf Causality Assessment Method (RUCAM) for DILI has been hindered by subjectivity and poor reliability. We sought to improve the RUCAM using data from the Drug-Induced Liver Injury Network (DILIN) and the Spanish DILI Registry, published literature, and iterative computer modeling. APPROACH AND RESULTS: RUCAM criteria were updated, clarified, and computerized. We removed criteria 3 (risk factors) for lack of added value and criteria 4 because we felt it more useful to assess each drug separately. Criteria 6 (drug-specific risk) was anchored to LiverTox likelihood scores. Iterative testing in subsets of 50-100 single-agent, nonherbal cases from both registries was done to optimize performance. We used classification tree analysis to establish diagnostic cutoffs for this revised electronic causality assessment method (RECAM) and compared RECAM with RUCAM for correlation with expert opinion diagnostic categories in 194 DILI cases (98 DILIN, 96 Spanish DILI). Area under receiver operator curves for identifying at least probable DILI were the same at 0.89 for RECAM and RUCAM. However, RECAM diagnostic categories have better observed overall agreement with expert opinion (0.62 vs. 0.56 weighted kappa, p = 0.14), and had better sensitivity to detect extreme diagnostic categories (73 vs. 54 for highly likely or high probable, p = 0.02; 65 vs. 48 for unlikely/excluded, p = 0.08) than RUCAM diagnostic categories. CONCLUSIONS: RECAM is an evidence-based update that is at least as capable as RUCAM in diagnosing DILI compared with expert opinion but is better than RUCAM at the diagnostic extremes. RECAM's increased objectivity and clarity will improve precision, reliability, and standardization of DILI diagnosis, but further refinement and validation in other cohorts are needed.


Funding Information: This publication is partially based on work from COSTAction “CA17112—Prospective European Drug‐Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology) www.cost.eu . MIL, ESB, GPA, AGJ, and RJA are members of COST Action CA17112. The authors thank Dr. Lauryna Aukštikalnė for her help in refining the online implementation of the RECAM. They also acknowledge the American Association for the Study of Liver Disease (AASLD) for supporting this research through the AASLD Innovations Fund (2016). Funding Information: Dr. Fontana received grants from AbbVie and Gilead. Dr. Aithal consults for Pfizer and GlaxoSmithKline. Dr. Hayashi is employed by the US Food and Drug Administration (FDA), but conclusions in this paper do not reflect any opinions of the FDA. The FDA has not evaluated the findings, assessments or conclusions in this paper. Funding Information: The Drug‐Induced Liver Injury (DILN) Network is structured as a U01 cooperative agreement with funds provided by the National Institute of Diabetes and Digestive and Kidney Diseases (U24‐DK065176, U01‐DK065201, U01‐DK065184, U01‐DK065211, U01DK065193, U01‐DK065238, U01‐DK083023, U01‐DK083027, U01‐DK082992, U01‐DK083020, and U01‐DK100928). Additional support is provided by CTSA grants (UL1 RR025761, UL1TR000083, UL1 RR024134, UL1 RR024986, UL1 RR024982, UL1 RR024150), the Intramural Research Program of the National Institutes of Health, the National Cancer Institute (ClinicalTrials.gov number: NCT00345930), and the 2016 American Association for the Study of Liver Disease (AASLD) Innovations Fund. The Spanish DILI Registry is funded by grants from Instituto de Salud Carlos III, cofounded by Fondo Europeo de Desarrollo Regional ‐ FEDER (PI 18/01804 and PT 20/00127) and Agencia Española del Medicamento. Plataforma ISCiii de Investigación Clínica and CIBERehd are funded by ISCIII Publisher Copyright: © 2022 American Association for the Study of Liver Diseases.

Files in this item

This item appears in the following Collection(s)