Comparison of two clinical scales for causality assessment in hepatotoxicity

This study was performed to compare the assessments of drug-induced liver i njury obtained with 2 methods, the Council for International Organizations of Medical Sciences (CIOMS) scale and the recently validated Maria & Victor ino (M&V) clinical scale, in cases submitted to a registry of hepatotoxicit y, A total of 215 cases of hepatotoxicity reported with a structured report ing form were evaluated by 3 independent experts. Because of the use of mul tiple drugs, 228 ratings were generated. The probability of the diagnosis w as classified as definitive, probable, possible, unlikely, or excluded, and evaluated for consistency with a weighted kappa statistical test. Absolute agreement between the 2 scales was observed in 42 cases (18%, weighted kap pa 0.28) with disagreement of 1 level in 108 cases (47%), and of 2 levels i n 70 cases (31%), The best correlation between the 2 scales was obtained fo r drug-induced liver injury involving a suggested immunoallergic mechanism: the disagreement was I level or less in 72% of the cases (34 of 48), compa red with 60% of the cases (85 of 141) that involved a presumed idiosyncrati c metabolic mechanism. The lowest agreement (6%) was observed in cases with evidence of cholestasis. No agreement was found in cases of fulminant hepa titis or death. The CIOMS scale showed better discriminative power and prod uced assessments closer to those of specialists. The performance of the M&V scale was poor in reactions with long latency periods (i.e,, amoxycillin/c lavulanic acid), evolution to chronicity after withdrawal (cholestatic patt ern), or death.