Liver and Bile
Hepatology. 2022;76(1):18–31
A revised electronic version of RUCAM for the diagnosis of DILI
Background and aims: Roussel Uclaf Causality Assessment Method (RUCAM) for drug-induced liver injury (DILI) has been hindered by subjectivity and poor reliability. The authors sought to improve the RUCAM using data from the DILI Network (DILIN) and the Spanish DILI Registry, published literature, and iterative computer modeling.
Approach and results: RUCAM criteria were updated, clarified, and computerized. The authors removed criteria 3 (risk factors) for lack of added value and criteria 4 because they 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, non-herbal cases from both registries was done to optimize performance. Classification tree analysis was used to establish diagnostic cut-offs 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-operating 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: The revised electronic causality assessment method (RECAM) is an evidence-based update that is at least as capable as Roussel Uclaf Causality Assessment Method (RUCAM) in diagnosing drug-induced liver injury 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.
DOI: 10.1002/hep.32327